Inflammatory Events Are Involved in Acne Lesion Initiation
Open accessAbstract
The earliest subclinical acne "lesion" is a microcomedone, of which hyperproliferation of the follicular epithelium is a characteristic feature. Inflammatory cells have been observed at the periphery of these "lesions". This study investigated whether inflammatory events occur pre or post hyperproliferative changes. Cellular, vascular, and proliferative markers were examined by immunohistochemical techniques on biopsies of clinically normal follicles from uninvolved skin and early inflamed lesions from acne patients. Control follicles were obtained from non-acne subjects. Follicles from uninvolved skin exhibited no microcomedonal features. Proliferation in the epithelium was comparable to controls and was significantly lower than in inflamed lesions. Numbers of CD3+, CD4+ T cells were elevated in the perifollicular and papillary dermis although levels were not equivalent to those in papules. The number of macrophages was also greatly increased and similar to those in papules. There were no changes in blood vessel numbers or vascular intercellular adhesion molecule 1 expression but E-selectin expression was increased to levels found in papules and vascular adhesion molecule 1 levels were upregulated. Levels of the pro-inflammatory cytokine interleukin-1 were also upregulated perifollicularly. Moreover, aberrant integrin expression was demonstrated in the epidermis around these uninvolved follicles and inflamed lesions whereas the basement membrane was still intact. These results provide novel evidence for vascular endothelial cell activation and involvement of inflammatory responses in the very earliest stages of acne lesion development.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Accumulation of lipid peroxides, specifically squalene peroxide, activates PPARs, stimulates keratinocyte proliferation and lipoxygenase activity, and overall increases the expression and secretion of proinflammatory cytokines in acne.
“Another interesting aspect of the detected changes is the accumulation of lipid peroxides, specifically squalene peroxide, which activates the Peroxisome Proliferator Activated Receptors (PPARs), stimulate keratinocyte proliferation and lipoxygenase (LOX) activity, overall increasing the expression and secretion of proinflammatory cytokines in acne.27-29”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [27]
Cites
Requirement of Vascular Integrin α <sub>v</sub> β <sub>3</sub> for Angiogenesis
Brooks, P. C., Clark, R. A. F., & Cheresh, D. A. (1994) · Science · doi:10.1126/science.7512751 · Cited by 3,020 · see citing works
Dustin, M. L., Rothlein, R., Bhan, A. K., Dinarello, C. A., & Springer, T. A. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.1.245 · Cited by 2,450 · see citing works
Interleukin-1 Type II Receptor: A Decoy Target for IL-1 That Is Regulated by IL-4
Colotta, F., Re, F., Muzio, M., Bertini, R., Polentarutti, N., Sironi, M., Giri, J. G., Dower, S., Sims, J. E., & Mantovani, A. (1993) · Science · doi:10.1126/science.8332913 · Cited by 979 · see citing works
Dustin, M. L., Singer, K. H., Tuck, D. T., & Springer, T. A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.4.1323 · Cited by 669 · see citing works
Keratins and the Keratinocyte Activation Cycle
Freedberg, I. M., Tomic‐Canic, M., Komine, M., & Blumenberg, M. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01327.x · Cited by 564 · see citing works
Detmar, M. J., Brown, L. F., Schön, M. P., Elicker, B. M., Velasco, P., Richard, L., Fukumura, D., Monsky, W. L., Claffey, K. P., & Jain, R. K. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00262.x · Cited by 550 · see citing works
Carroll, J. M., Romero, M. R., & Watt, F. M. (1995) · Cell · doi:10.1016/0092-8674(95)90211-2 · Cited by 303 · see citing works
Essential fatty acids and acne
Downing, D. T., Stewart, M. E., Wertz, P. W., & Strauss, J. S. (1986) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(86)70025-x · Cited by 261 · see citing works
Elias, P. M., Brown, B. E., & Ziboh, V. A. (1980) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12541775 · Cited by 257 · see citing works
The Leeds revised acne grading system
O'brien, S., Lewis, J. B., & Cunliffe, W. (1998) · Journal of Dermatological Treatment · doi:10.3109/09546639809160698 · Cited by 226 · see citing works
Self-citationEndothelial leucocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation
Groves, R. W., Allen, M. H., Barker, J. N., Haskard, D. O., & MACDONALD, D. M. (1991) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1991.tb00419.x · Cited by 209 · see citing works
A histological and immunocytochemical study of early acne lesions
Norris, J. F. B., & Cunliffe, W. J. (1988) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1988.tb02566.x · Cited by 204 · see citing works
Self-citationUltrastructural Observations in Acne Vulgaris: the Normal Sebaceous Follicle and Acne Lesions
Knutson, D. D. (1974) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12676804 · Cited by 203 · see citing works
Distinctive Integrin Expression in the Newly Forming Epidermis During Wound Healing in Humans
Cavani, A., Zambruno, G., Marconi, A., Manca, V., Marchetti, M., & Giannetti, A. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12366057 · Cited by 198 · see citing works
Guy, R., Green, M. R., & Kealey, T. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12329907 · Cited by 190 · see citing works
Ingham, E., Eady, E. A., Goodwin, C. E., Cove, J. H., & Cunliffe, W. J. (1992) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12460324 · Cited by 188 · see citing works
Self-citationGroves, R. W., Allen, M. H., Ross, E. L., Barker, J. N., & MACDONALD, D. M. (1995) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1995.tb08666.x · Cited by 173 · see citing works
Comedogenesis: some new aetiological, clinical and therapeutic strategies
Cunliffe, W. J., Holland, D. B., Clark, S. M., & Stables, G. I. (2000) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2000.03531.x · Cited by 159 · see citing works
Self-citationWEBSTER, G. F. (1995) · Journal of the American Academy of Dermatology · doi:10.1016/0190-9622(95)90243-0 · Cited by 157 · see citing works
Cellular dynamics of comedo formation in acne vulgaris
Plewig, G., Fulton, J. E., & Kligman, A. M. (1971) · Archives of Dermatological Research · doi:10.1007/bf00595286 · Cited by 132 · see citing works
Effect of In Vivo Interleukin-1 on Adhesion Molecule Expression in Normal Human Skin
Groves, R. W., Ross, E. L., Barker, J. N. W. N., Ross, J., Camp, R. D. R., & MACDONALD, D. M. (1992) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12499816 · Cited by 102 · see citing works
Quantification of Cellular Proliferation in Acne Using the Monoclonal Antibody Ki-67
Knaggs, H. E., Holland, D. B., Morris, C., Wood, E. J., & Cunliffe, W. J. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371738 · Cited by 101 · see citing works
Self-citationImmunohistochemical investigation of evolving inflammation in lesions of acne vulgaris
Layton, A., Morris, C., Cunliffe, W. J., & Ingham, E. (1998) · Experimental Dermatology · doi:10.1111/j.1600-0625.1998.tb00323.x · Cited by 74 · see citing works
Self-citationThe Effects of Inflammatory Cytokines on the Isolated Human Sebaceous Infundibulum
Guy, R., & Kealey, T. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00143.x · Cited by 71 · see citing works
Perisho, K., Wertz, P. W., Madison, K. C., Stewart, M. E., & Downing, D. T. (1988) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12456327 · Cited by 65 · see citing works
Groves, R. W., Sherman, L., Mizutani, H., Dower, S., & Kupper, T. S. (1994) · PubMed Central · Cited by 63 · see citing works
Barrier function coordinately regulates epidermal IL‐1 and IL‐1 receptor antagonist mRNA levels
Wood, L. C., Feingold, K. R., Sequeira‐Martin, S. M., Elias, P. M., & Grünfeld, C. (1994) · Experimental Dermatology · doi:10.1111/j.1600-0625.1994.tb00047.x · Cited by 62 · see citing works
Altered vascular endothelium integrin expression in psoriasis.
Creamer, D., Allen, M., Sousa, A. R., Poston, R. N., & Barker, J. N. (1995) · Europe PMC (PubMed Central) · Cited by 45 · see citing works
Variation in Pilosebaceous Duct Keratinocyte Proliferation in Acne Patients
Aldana, O. L., Holland, D. B., & Cunliffe, W. J. (1998) · Dermatology · doi:10.1159/000017839 · Cited by 33 · see citing works
Self-citationHerzinger, T. (1996) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(96)90740-9 · Cited by 30 · see citing works
Kozłowska, U., Blume‐Peytavi, U., Kodelja, V., Sommer, C., Goerdt, S., Jabłońska, S., & Orfanos, C. E. (1998) · Dermatology · doi:10.1159/000017878 · Cited by 21 · see citing works
The Natural Evolution of Comedones Into Inflammatory Papules and Pustules
Orentreich∥, N., & Durr, N. P. (1974) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12724274 · Cited by 20 · see citing works
Post-transcriptional regulation of E2A proteins via lipopolysaccharide and CD40 signaling
Meyer, K. B., & Mufti, D. A. H. (2000) · European Journal of Immunology · doi:10.1002/1521-4141(200002)30:2 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 34 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Grice, E. A., & Segre, J. A. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2537 · Cited by 3,143 · see citing works
Williams, H. C., Dellavalle, R. P., & Garner, S. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60321-8 · Cited by 1,126 · see citing works
Thiboutot, D. M., Gollnick, H. P. M., Bettoli, V., Dréno, B., Kang, S., Leyden, J. J., Shalita, A. R., Lozada, V. T., Berson, D. S., Finlay, A. Y., et al. (2009) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2009.01.019 · Cited by 839 · see citing works
“These researchers hypothesize that the subsequent production of cytokines activates local endothelial cells, up-regulating inflammatory vascular markers (E-selectin, vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and human leukocyte antigen-DR [HLA-DR]) in the vasculature aroun…”
BackgroundInfluentialAcne and sebaceous gland function
Zouboulis, C. C. (2004) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2004.03.004 · Cited by 561 · see citing works
Tuchayi, S. M., Makrantonaki, E., Ganceviciene, R., Dessinioti, C., Feldman, S. R., & Zouboulis, C. C. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.29 · Cited by 432 · see citing works
Steroidogenesis in the skin: Implications for local immune functions
Slominski, A., Zbytek, B., Nikolakis, G., Manna, P. R., Skobowiat, C., Zmijewski, M., Li, W., Janjetovic, Z., Postlethwaite, A., Zouboulis, C. C., et al. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.006 · Cited by 369 · see citing works
Nagy, I., Pivarcsi, A., Kis, K., Koreck, A., Bodai, L., McDowell, A., Seltmann, H., Patrick, S., Zouboulis, C. C., & Kemény, L. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2006.04.001 · Cited by 375 · see citing works
“Macrophages, T cells, keratinocytes and sebocytes are all likely to be involved in the formation of acne lesions [6,15,16,39,40].”
BackgroundWhat is new in the pathophysiology of acne, an overview
Dréno, B. (2017) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.14374 · Cited by 382 · see citing works
Nagy, I., Pivarcsi, A., Koreck, A., Széll, M., Urbán, E. Z., & Kemény, L. V. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23705.x · Cited by 336 · see citing works
An update on the role of the sebaceous gland in the pathogenesis of acne
Makrantonaki, E., Gancevičienė, R., & Zouboulis, C. C. (2011) · Dermato-Endocrinology · doi:10.4161/derm.3.1.13900 · Cited by 301 · see citing works
Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris
O’Neill, A. M., & Gallo, R. L. (2018) · Microbiome · doi:10.1186/s40168-018-0558-5 · Cited by 334 · see citing works
Alestas, T., Ganceviciene, R., Fimmel, S., Müller-Decker, K., & Zouboulis, C. C. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0715-8 · Cited by 269 · see citing works
“phages in early non-inflammatory acne lesions [3] support a major role of genuine inflammatory signalling in acne [4, 5].”
BackgroundThe role of Propionibacterium acnes in acne pathogenesis: facts and controversies
Dessinioti, C., & Katsambas, A. (2009) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2009.03.012 · Cited by 261 · see citing works
Propionibacterium acnes : an update on its role in the pathogenesis of acne
Beylot, C., Auffret, N., Poli, F., Claudel, J. P., Leccia, M. ‐., Giudice, P. D., & Dréno, B. (2013) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12224 · Cited by 254 · see citing works
Kang, S., Cho, S., Chung, J. H., Hammerberg, C., Fisher, G. J., & Voorhees, J. J. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62479-0 · Cited by 251 · see citing works
“Thus, the recent observation that ICAM-1, E-selectin, and VCAM-1 expression levels on the luminal surface of endothelial cells are increased in inflammatory acne papules may be a consequence of TNF-# and IL-1$ induction in the milieu.(31) The elaboration of adhesion molecules is necessary to slow the flow of circulati…”
BackgroundAcne is an inflammatory disease and alterations of sebum composition initiate acne lesions
Zouboulis, C. C., Jourdan, E., & Picardo, M. (2014) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12298 · Cited by 286 · see citing works
IL-1β Drives Inflammatory Responses to Propionibacterium acnes In Vitro and In Vivo
Kistowska, M., Gehrke, S., Jankovic, D. L., Kerl, K., Fettelschoss‐Gabriel, A., Feldmeyer, L., Fenini, G., Kolios, A. G. A., Navarini, A. A., Gancevičienė, R., et al. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.438 · Cited by 239 · see citing works
“Previous studies histologically assessing early events in skin biopsies from acne patients have revealed that macrophages are present in high numbers in the immediate proximity of the pilo-sebaceous follicle of uninvolved acne skin as well as in early stage inflammatory lesions (Layton et al., 1998; Jeremy et al., 200…”
BackgroundMcLaughlin, J. B., Watterson, S., Layton, A., Bjourson, A. J., Barnard, E., & McDowell, A. (2019) · Microorganisms · doi:10.3390/microorganisms7050128 · Cited by 233 · see citing works
“In particular, formation of microcomedones is preceded by a lymphocytic infiltrate consisting of CD4+ T cells and CD68+ macrophages [46]; inflammation is, therefore, not initiated by neutrophils (as originally thought), which appear later in the process and lead to pustule formation [47].”
BackgroundIL-17/Th17 Pathway Is Activated in Acne Lesions
Kelhälä, H., Palatsi, R., Fyhrquist, N., Lehtimäki, S., Väyrynen, J. P., Kallioinen, M. J., Kubin, M. E., Greco, D., Tasanen, K., Alenius, H. T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105238 · Cited by 217 · see citing works
“The formation of microcomedos is preceded by mononuclear infiltrates consisting mainly of CD4+ T-cells and CD68+ macrophages [3].”
BackgroundDréno, B., Khammari, A., Orain, N., Noray, C., Merial‐Kieny, C., Méry, S., & Nocera, T. (2006) · Dermatology · doi:10.1159/000096912 · Cited by 217 · see citing works
von Laffert, M., Helmbold, P., Wohlrab, J., Fiedler, E., Stadie, V., & Marsch, W. C. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00915.x · Cited by 206 · see citing works
Trivedi, N. R., Gilliland, K. L., Zhao, W., Liu, W., & Thiboutot, D. M. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700213 · Cited by 196 · see citing works
“(Freedberg et al., 2001; Jeremy et al., 2003).”
The role of inflammation in the pathology of acne.
Tanghetti, E. A. (2013) · Europe PMC (PubMed Central) · Cited by 186 · see citing works
Propionibacterium acnes Promotes Th17 and Th17/Th1 Responses in Acne Patients
Kistowska, M., Meier-Schiesser, B., Proust, T., Feldmeyer, L., Cozzio, A., Kuendig, T., Contassot, E., & French, L. E. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.290 · Cited by 188 · see citing works
Understanding innate immunity and inflammation in acne: implications for management
Dréno, B., Gollnick, H. P. M., Kang, S., Thiboutot, D. M., Bettoli, V., Torres, V., Leyden, J., & the Global Alliance to Improve Outcomes in Acne (2015) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13190 · Cited by 181 · see citing works
Ottaviani, M., Alestas, T., Flori, E., Mastrofrancesco, A., Zouboulis, C. C., & Picardo, M. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700434 · Cited by 175 · see citing works
“acnes (Yokomizo et al., 2001; Jeremy et al., 2003).”
Ozolins, M., Eady, E. A., Avery, A. J., Cunliffe, W. J., Li Wan Po, A., O'Neill, C., Simpson, N. B., Walters, C. E., Carnegie, E., Lewis, J. B., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17591-0 · Cited by 168 · see citing works
Self-citationWhy Topical Retinoids Are Mainstay of Therapy for Acne
Leyden, J., Stein-Gold, L., & Weiss, J. (2017) · Dermatology and Therapy · doi:10.1007/s13555-017-0185-2 · Cited by 164 · see citing works
Skin Immune Landscape: Inside and Outside the Organism
Abdallah, F., Mijouin, L., & Pichon, C. (2017) · Mediators of Inflammation · doi:10.1155/2017/5095293 · Cited by 170 · see citing works
“Acne pathogenesis initiates and propagates due to abnormal keratinization resulting in pilosebaceous inflammation [147].”
BackgroundInteractions between host factors and the skin microbiome
SanMiguel, A. J., & Grice, E. A. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1812-z · Cited by 168 · see citing works
Potential role of F ox O 1 and m TORC 1 in the pathogenesis of W estern diet‐induced acne
Melnik, B. C., & Zouboulis, C. C. (2013) · Experimental Dermatology · doi:10.1111/exd.12142 · Cited by 163 · see citing works
Recent Advances in Acne Pathogenesis: Implications for Therapy
Das, S., & Reynolds, R. V. (2014) · American Journal of Clinical Dermatology · doi:10.1007/s40257-014-0099-z · Cited by 157 · see citing works
“Androgens also promote comedogenesis through regulation of growth factors and IL-1a, which stimulate hyperkeratinization within the follicular duct and infundibulum [28].”
BackgroundInfluentialPatients with Acne Vulgaris Have a Distinct Gut Microbiota in Comparison with Healthy Controls
Deng, Y., Wang, H., Zhou, J. W., Mou, Y., Wang, G., & Xiong, X. (2018) · Acta Dermato Venereologica · doi:10.2340/00015555-2968 · Cited by 158 · see citing works
“Inflammatory markers, such as IL-1, TNF-α, IL-6, and IL-8, were present in the early microcomedones and inflamed lesions (31), suggesting that disorder of gut microbiota caused by Western dietary habits could contribute to the early inflammation in acne.”
BackgroundDisorders of the Sebaceous Glands
Simpson, N. B., & Cunliffe, W. J. (2004) · doi:10.1002/9780470750520.ch43 · Cited by 155 · see citing works
Self-citationPhotodynamic therapy for acne vulgaris: A critical review from basics to clinical practice
Sakamoto, F. H., Lopes, J. D., & Anderson, R. R. (2010) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2009.09.056 · Cited by 150 · see citing works
Sebaceous-immunobiology is orchestrated by sebum lipids
Lovászi, M., Szegedi, A., Zouboulis, C. C., & Törőcsik, D. (2017) · Dermato-Endocrinology · doi:10.1080/19381980.2017.1375636 · Cited by 151 · see citing works
Topical Retinoids in Acne Vulgaris
Thielitz, A., & Gollnick, H. P. M. (2008) · American Journal of Clinical Dermatology · doi:10.2165/0128071-200809060-00003 · Cited by 145 · see citing works
Melnik, B. (2012) · Dermato-Endocrinology · doi:10.4161/derm.19828 · Cited by 88 · see citing works
“T cell infiltrates are found in early acne lesions, which are associated with increased synthesis of interleukin-1a of acneprone sebaceous follicles.(76) Thus, the question arises whether Western diet-mediated mTORC1-overactivity affects T-cell homeostasis and the regulation of inflammatory immune responses in acne.”
BackgroundAcne, Microbiome, and Probiotics: The Gut–Skin Axis
Sánchez-Pellicer, P., Navarro-Moratalla, L., Núñez-Delegido, E., Ruzafa-Costas, B., Agüera-Santos, J., & Navarro-López, V. (2022) · Microorganisms · doi:10.3390/microorganisms10071303 · Cited by 137 · see citing works
“An infiltration of CD4 cells has been evidenced in the pilosebaceous follicle in the initial stages of acne; CD3, CD4, and macrophage cells were found from the beginning of formation of the microcomedone [91].”
BackgroundAzelaic Acid: Properties and Mode of Action
Sieber, M. A., & Hegel, J. K. E. (2013) · Skin Pharmacology and Physiology · doi:10.1159/000354888 · Cited by 135 · see citing works
Clinical applications of non-antimicrobial tetracyclines in dermatology
Monk, E., Shalita, A. R., & Siegel, D. M. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.10.007 · Cited by 132 · see citing works
Hammer, K. A. (2014) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2014.10.011 · Cited by 132 · see citing works
European recommendations on the use of oral antibiotics for acne.
Dréno, B., Bettoli, V., Ochsendorf, F. R., Layton, A., Mobacken, H., & Degreef, H. J. (2004) · PubMed · Cited by 129 · see citing works
Zouboulis, C. C., Coenye, T., He, L., Kabashima, K., Kobayashi, T., Niemann, C., Nomura, T., Oláh, A., Picardo, M., Quist, S., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1029818 · Cited by 134 · see citing works
“…response, fi rst published in 2001 (88) obtained partial con fi rmation in 2003 through the detection of CD3+, CD4+ T cells in the perifollicular dermis of acne microcomedones before even the initiation of sebocyte and follicular keratinocyte hyperproliferation, associated with the acne lesions (89).”
BackgroundDegitz, K., Placzek, M., Borelli, C., & Plewig, G. (2007) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0387.2007.06274.x · Cited by 126 · see citing works
The role of topical dermocosmetics in acne vulgaris
Araviiskaia, E., & Dréno, B. (2016) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13579 · Cited by 123 · see citing works
Role of hormones in acne vulgaris
Arora, M. K., Yadav, A., & Saini, V. (2011) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2011.06.984 · Cited by 121 · see citing works
“The entire process is initiated by interleukin (IL)-1α, which is up-regulated in response to a relative linoleic acid deficiency caused by excess sebum and perturbation of barrier function within the follicle [16].”
BackgroundPavicic, T., Wollenweber, U., Farwick, M., & Korting, H. C. (2007) · International Journal of Cosmetic Science · doi:10.1111/j.1467-2494.2007.00378.x · Cited by 120 · see citing works
“Recently, significant pro-inflammatory factors, such as interleukin-1, have been identified around clinically normal pilosebaceous follicles from uninvolved skin in acne patients prior to hyperproliferation of the follicular epithelium [1].”
BackgroundBernstein, C. N., Nugent, Z., Longobardi, T., & Blanchard, J. F. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.417 · Cited by 118 · see citing works
Ottaviani, M., Camera, E., & Picardo, M. (2010) · Mediators of Inflammation · doi:10.1155/2010/858176 · Cited by 143 · see citing works
Comedone formation: Etiology, clinical presentation, and treatment
Cunliffe, W. J., Holland, D. B., & Jeremy, A. H. T. (2004) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2004.03.011 · Cited by 116 · see citing works
Self-citationSchaller, M., Loewenstein, M., Borelli, C., Jacob, K., Vogeser, M., Burgdorf, W. H. C., & Plewig, G. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06530.x · Cited by 116 · see citing works
Farrar, M. D., & Ingham, E. (2004) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2004.03.006 · Cited by 114 · see citing works
The Role of Photodynamic Therapy in Acne: An Evidence-Based Review
Boen, M., Brownell, J., Patel, P., & Tsoukas, M. M. (2017) · American Journal of Clinical Dermatology · doi:10.1007/s40257-017-0255-3 · Cited by 111 · see citing works
Adult-onset acne: prevalence, impact, and management challenges
Rocha, M., & Bagatin, E. (2018) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s137794 · Cited by 110 · see citing works
“20 P. acnes is connected to toll-like receptors (TLRs) present in the keratinocytes, sebocytes, and dendritic cells, triggering signalizing cascades that activate transcriptional factors such as nuclear factor kappa B and phosphokinases such as mitogen activators.”
Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies
Kim, H. J., & Kim, Y. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105302 · Cited by 132 · see citing works
The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies
Rigopoulos, D., Larios, G., & Katsambas, A. (2009) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2009.03.005 · Cited by 105 · see citing works
Zouboulis, C. C., Schagen, S., & Alestas, T. (2008) · Archives of Dermatological Research · doi:10.1007/s00403-008-0879-5 · Cited by 104 · see citing works
Resveratrol-Containing Gel for the Treatment of Acne Vulgaris
Fabbrocini, G., Staibano, S., Rosa, G. D., Battimiello, V., Fardella, N., Ilardi, G., Rotonda, M. I. L., Longobardi, A., Mazzella, M., Siano, M., et al. (2011) · American Journal of Clinical Dermatology · doi:10.2165/11530630-000000000-00000 · Cited by 104 · see citing works
Adolescent acne vulgaris: current and emerging treatments
Layton, A., & Ravenscroft, J. (2022) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(22)00314-5 · Cited by 103 · see citing works
Castillo, D. E., Nanda, S., & Keri, J. E. (2018) · Dermatology and Therapy · doi:10.1007/s13555-018-0275-9 · Cited by 103 · see citing works
Update on etiopathogenesis and treatment of Acne
Bhat, Y. J., Latief, I., & Hassan, I. (2017) · Indian Journal of Dermatology Venereology and Leprology · doi:10.4103/0378-6323.199581 · Cited by 100 · see citing works
New Insights into Acne Pathogenesis: Propionibacterium Acnes Activates the Inflammasome
Contassot, E., & French, L. E. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.505 · Cited by 98 · see citing works
“tory cells, and notably macrophages, likely serving as sentinels, are present in high numbers in the immediate proximity of pilo-sebaceous follicles of the uninvolved acne skin, as well as in early stage inflammatory acne lesions, but in contrast, not around the pilosebaceous units of normal skin from healthy individu…”
BackgroundVasanth, S., Dubey, A., Shriram, R. G., Lewis, S. A., Ghate, V., El‐Zahaby, S. A., & Hebbar, S. (2020) · AAPS PharmSciTech · doi:10.1208/s12249-019-1518-5 · Cited by 101 · see citing works
Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis
Kurokawa, I., Layton, A., & Ogawa, R. (2021) · Dermatology and Therapy · doi:10.1007/s13555-021-00552-6 · Cited by 96 · see citing works
Update in retinoid therapy of acne
Thielitz, A., Krautheim, A., & Gollnick, H. P. M. (2006) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2006.00084.x · Cited by 96 · see citing works
“On a microscopic level, the beginning of microcomedone formation is also associated with vascular endothelial cell activation and inflammatory events (7), which support the hypothesis that acne may represent a genuine inflammatory disease.”
BackgroundZhou, B., Zhang, J.-A., Zhang, Q., Permatasari, F., Xu, Y., Wu, D., Yin, Z., & Luo, D. (2013) · Mediators of Inflammation · doi:10.1155/2013/530429 · Cited by 94 · see citing works
“Thus, the observation that ICAM-1, E-selectin, and VCAM1 expression levels on the luminal surface of endothelial cells are increased in inflammatory acne papules may be a consequence of TNF-α and IL-1β induction in themilieu [33].”
BackgroundSebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells
Mattii, M., Lovászi, M., Garzorz, N., Atenhan, A., Quaranta, M., Lauffer, F., Konstantinow, A., Küpper, M., Zouboulis, C. C., Kemény, L. V., et al. (2017) · British Journal of Dermatology · doi:10.1111/bjd.15879 · Cited by 93 · see citing works
Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process
Dagnelie, M., Corvec, S., Saint-Jean, M., Nguyen, J., Khammari, A., & Dréno, B. (2019) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.15795 · Cited by 96 · see citing works
Moon, J., Yoon, J. Y., Yang, J. H., Kwon, H. H., Min, S., & Suh, D. H. (2019) · British Journal of Dermatology · doi:10.1111/bjd.17851 · Cited by 92 · see citing works
Katsambas, A., & Papakonstantinou, A. (2004) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2004.03.014 · Cited by 92 · see citing works
Picardo, M., Eichenfield, L. F., & Tan, J. K. L. (2017) · Dermatology and Therapy · doi:10.1007/s13555-016-0168-8 · Cited by 90 · see citing works
“These include a confirmed association between sebaceous lipid synthesis and inflammation [8] and evidence of elevated levels of CD3? and CD4? T cells and inflammatory markers in early subclinical acne lesions (microcomedones) [9, 10].”
BackgroundToll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne
Selway, J. L., Kurczab, T., Kealey, T., & Langlands, K. (2013) · BMC Dermatology · doi:10.1186/1471-5945-13-10 · Cited by 90 · see citing works
“Thus, enhanced sebum levels, high IGF1 signaling and free fatty acid availability could act in concert to create a pro-inflammatory state primed for comedogenesis [28].”
BackgroundDisorders of the Sebaceous Glands
Layton, A. (2010) · Wiley eBooks · doi:10.1002/9781444317633.ch42 · Cited by 87 · see citing works
Dainichi, T., Hanakawa, S., & Kabashima, K. (2014) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2014.08.010 · Cited by 89 · see citing works
“[31] Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ: Inflammatory events are involved in acne lesion initiation.”
BackgroundCallender, V. D., Baldwin, H. E., Cook-Bolden, F. E., Alexis, A. F., Gold, L. S., & Guenin, E. (2021) · American Journal of Clinical Dermatology · doi:10.1007/s40257-021-00643-2 · Cited by 87 · see citing works
“, increased expression of vascular adhesion molecule 1, upregulation of interleukin-1) are likely involved in the very earliest stages of acne development, prior to the hyperproliferative changes that are seen in visible lesions [45].”
BackgroundThe Role of Inflammation in the Pathogenesis of Acne and Acne Scarring
Holland, D. B., & Jeremy, A. H. T. (2005) · Seminars in Cutaneous Medicine and Surgery · doi:10.1016/j.sder.2005.03.004 · Cited by 87 · see citing works
Self-citationFrew, J. W. (2020) · JAAD International · doi:10.1016/j.jdin.2020.05.005 · Cited by 84 · see citing works
Nakatsuji, T., Liu, Y.-T., Huang, C.-P., Gallo, R. L., & Huang, C. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.117 · Cited by 86 · see citing works
“The first stage is comedo formation, which is characterized by the initiation of inflammatory events before hyperproliferation of the follicular epithelia (microcomedo) (Jeremy et al., 2003); the second stage is the occurrence of inflammation and disruption of follicular epithelia.”
BackgroundThe Pathogenesis and Management of Acne-Induced Post-inflammatory Hyperpigmentation
Elbuluk, N., Grimes, P. E., Chien, A. L.-L., Hamzavi, I. H., Alexis, A. F., Taylor, S. C., González, N., Weiss, J., Desai, S. R., & Kang, S. (2021) · American Journal of Clinical Dermatology · doi:10.1007/s40257-021-00633-4 · Cited by 92 · see citing works
Thielitz, A., Reinhold, D., Vetter, R., Bank, U., Helmuth, M., Hartig, R., Wrenger, S., Wiswedel, I., Lendeckel, U., Kähne, T., et al. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700439 · Cited by 82 · see citing works
“Increased levels can be found in uninvolved follicles, early acne lesions (Aldana et al., 1998; Jeremy et al., 2003), and abundantly in extracted mature comedones (Ingham et al.”
BackgroundOmer, H., McDowell, A., & Alexeyev, O. A. (2016) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2016.10.003 · Cited by 82 · see citing works
IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art
Bernardini, N., Skroza, N., Tolino, E., Mambrin, A., Anzalone, A., Balduzzi, V., Colapietra, D., Marchesiello, A., Michelini, S., Proietti, I., et al. (2019) · International Journal of Dermatology · doi:10.1111/ijd.14695 · Cited by 80 · see citing works
Choi, E.-J., Lee, H. G., Bae, I., Kim, W., Park, J., Lee, T. R., & Cho, E. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.01.007 · Cited by 79 · see citing works
“Increased numbers of neutrophils, hyperkeratinization, and less desquamation are frequently observed in acne lesions (Gollnick et al., 2003; Jeremy et al., 2003).”
BackgroundUse of lipidomics to investigate sebum dysfunction in juvenile acne
Camera, E., Ludovici, M., Tortorella, S., Sinagra, J. L., Capitanio, B., Goracci, L., & Picardo, M. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m067942 · Cited by 79 · see citing works
Mias, C., Mengeaud, V., Bessou‐Touya, S., & Duplan, H. (2023) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.18794 · Cited by 84 · see citing works
“25 It is now known that inflammation not only occurs during the development of the inflammatory phase but also during the initial phases of the pathology, in microcomedones and comedones.(19,26) These four pathways have been reviewed elsewhere.”
BackgroundManagement of Acne Scarring, Part II
Levy, L., & Zeichner, J. (2012) · American Journal of Clinical Dermatology · doi:10.2165/11631410-000000000-00000 · Cited by 77 · see citing works
Jarrousse, V., Castex‐Rizzi, N., Khammari, A., Charvéron, M., & Dréno, B. (2007) · Archives of Dermatological Research · doi:10.1007/s00403-007-0774-5 · Cited by 76 · see citing works
“Concerning 3 and 6 integrins, an in vivo study focusing on follicles of acne patients [7] has shown an aberrant 2 and 3 integrins expression around comedones and uninvolved pilosebaceous follicles from acne lesions.”
BackgroundEndocrinology and immunology of acne: Two sides of the same coin
Zouboulis, C. C. (2020) · Experimental Dermatology · doi:10.1111/exd.14172 · Cited by 76 · see citing works
The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris
Gancevičienė, R., Böhm, M., Fimmel, S., & Zouboulis, C. C. (2009) · Dermato-Endocrinology · doi:10.4161/derm.1.3.8496 · Cited by 74 · see citing works
Role of FGFR2-signaling in the pathogenesis of acne
Melnik, B. C. (2009) · Dermato-Endocrinology · doi:10.4161/derm.1.3.8474 · Cited by 74 · see citing works
Systemic antibiotic therapy of acne vulgaris
Ochsendorf, F. R. (2006) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0387.2006.06053.x · Cited by 74 · see citing works
Could adult female acne be associated with modern life?
Albuquerque, R. G., Rocha, M., Bagatin, E., Tufik, S., & Andersen, M. L. (2014) · Archives of Dermatological Research · doi:10.1007/s00403-014-1482-6 · Cited by 74 · see citing works
“Even more, the number of cells was equivalent to that observed on inflamed lesions (acne-involved skin) from the same patient [38].”
BackgroundA microbial aetiology of acne: what is the evidence?
Shaheen, B., & Gonzalez, M. (2011) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2011.10375.x · Cited by 72 · see citing works
Anti-Acne Agents Attenuate FGFR2 Signal Transduction in Acne
Melnik, B. C., Schmitz, G., & Zouboulis, C. C. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.8 · Cited by 72 · see citing works
“IL-1a is involved in the early inflammatory events in acne and activation of keratinocytes and sebocytes (Anttila et al., 1992; Boehm et al. 1995; Zouboulis et al., 1998; Freedberg et al., 2001; Jeremy et al., 2003).”
BackgroundPathogenesis of acne vulgaris: recent advances.
Bhambri, S., Rosso, J. Q. D., & Bhambri, A. (2009) · PubMed · Cited by 71 · see citing works
Sugisaki, H., Yamanaka, K., Kakeda, M., Kitagawa, H., Tanaka, K. Y., Watanabe, K., Gabazza, E. C., Kurokawa, I., & Mizutani, H. (2009) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2009.02.015 · Cited by 71 · see citing works
Propionic Acid Produced by Propionibacterium acnes Strains Contributes to Their Pathogenicity
Tax, G., Urbán, E. Z., Palotás, Z., Puskas, R., Kónya, Z., Bı́ró, T., Kemény, L. V., & Szabó, K. (2015) · Acta Dermato Venereologica · doi:10.2340/00015555-2154 · Cited by 71 · see citing works
A review of skin immune processes in acne
Jin, Z., Song, Y., & He, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1324930 · Cited by 77 · see citing works
Thy, T., Zarkhin, S., Orringer, J. S., Nemeth, S. A., Hamilton, T. A., Sachs, D. L., Voorhees, J. J., & Kang, S. (2008) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2007.12.024 · Cited by 70 · see citing works
- Authors
- Jeremy, A. H. T., Holland, D. B., Roberts, S. G., Thomson, K. F., & Cunliffe, W. J.
- Affiliations
- Leeds General Infirmary (GB)
- Corresponding author
- Holland, Diana B.
- ORCID
- Cunliffe, William J.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 121
- Issue
- 1
- Pages
- 20-27
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2062768474
- Cited by
- 541
- References
- 34
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 52 · 2023: 28 · 2022: 20 · 2021: 28 · 2020: 26 · 2019: 32 · 2018: 29 · 2017: 24 · 2016: 23 · 2015: 19 · 2014: 35 · 2013: 27 · 2012: 17
- FWCI
- 16.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- acne, microcomedones, inflammation, T cells, macrophages, endothelial activation, E-selectin, VCAM-1, interleukin-1, integrins, basement membrane, follicular epithelium, vascular adhesion molecules
- MeSH terms
- CD68 Molecule, Acne Vulgaris, Adolescent, Adult, Blood Vessels, Cell Differentiation, Cell Division, HLA-DR Antigens, Humans, Immunohistochemistry, Immunologic Memory, Interleukin-1, Laminin, Langerhans Cells, Macrophages, Neutrophils, Antigens, Differentiation, Myelomonocytic, Biomarkers, CD4-Positive T-Lymphocytes, Keratinocytes, Antigens, CD, CD3 Complex, Receptors, Interleukin-1, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Hair Follicle, Antigens, CD1, Collagen Type IV, Integrin alpha6, Receptors, Interleukin-1 Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
