Serum amyloid A opposes lipoxin A 4 to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease
Open accessAbstract
Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A 4 (LXA 4 ) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA 2 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA 4 . Human lung macrophages (CD68 + ) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC 50 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA 4 but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Increase in serum level of SAA is associated with glucocorticoid resistance.
“A recent article reported that the increase in the serum level of serum amyloid A (SAA) is associated with glucocorticoid resistance [6].”
From Picroside II Isolated from Pseudolysimachion rotundum var. subintegrum Inhibits Glucocorticoid Refractory Serum Amyloid A (SAA) Expression and SAA-induced IL-33 Secretion (2019) · cites this paper as [6]
The Abstract (page not provided) reports increased circulating SAA during COPD exacerbations and identifies SAA as a candidate mediator of glucocorticoid-refractory lung inflammation. It does not establish that higher serum SAA levels themselves are associated with measured glucocorticoid resistance; the resistance findings concern lung inflammation and local SAA production. (LLM, conf=0.83)
Experimental — accuracy not yet measuredDEX induces SAA expression on its own and synergistically increases LPS-induced SAA expression in THP-1 cells.
“It has been shown that DEX induces SAA expression on its own and synergistically increases LPS-induced SAA expression in THP-1 cells [6].”
SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation.
“It has been shown that SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation [6,15].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cytokine-mediated regulation of CXCR4 expression in human neutrophils
Nagase, H., Miyamasu, M., Yamaguchi, M., Imanishi, M., Tsuno, N. H., Matsushima, K., Yamamoto, K., Morita, Y., & Hirai, K. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.4.711 · Cited by 4,713 · see citing works
Resolution of inflammation: the beginning programs the end
Serhan, C. N., & Savill, J. (2005) · Nature Immunology · doi:10.1038/ni1276 · Cited by 2,552 · see citing works
Burden and clinical features of chronic obstructive pulmonary disease (COPD)
PAUWELS, R. A., & Rabe, K. F. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16855-4 · Cited by 1,005 · see citing works
Glucocorticoid resistance in inflammatory diseases
Barnes, P. J., & Adcock, I. M. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60326-3 · Cited by 983 · see citing works
Effects of cigarette smoke on the human airway epithelial cell transcriptome
Spira, A. E., Beane, J., Shah, V., Liu, G., Schembri, F. M., Yang, X., Palma, J. F., & Brody, J. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401422101 · Cited by 618 · see citing works
The Lipoxin Receptor ALX: Potent Ligand-Specific and Stereoselective Actions in Vivo
Chiang, N., Serhan, C. N., Dahlén, S., Drazen, J. M., Hay, D. W. P., Rovati, G. E., Shimizu, T., Yokomizo, T., & Brink, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.4 · Cited by 464 · see citing works
Perretti, M., Chiang, N., La, M., Fierro, I. M., Marullo, S., Getting, S. J., Solito, E., & Serhan, C. N. (2002) · Nature Medicine · doi:10.1038/nm786 · Cited by 449 · see citing works
Su, S. B., Gong, W., Gao, J., Shen, W., Murphy, P. M., Oppenheim, J. J., & Wang, J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.2.395 · Cited by 430 · see citing works
Hurst, J. R., Perera, W. R., Wilkinson, T. M. A., Donaldson, G. C., & Wedzicha, J. A. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200505-704oc · Cited by 346 · see citing works
Culpitt, S. V., Rogers, D. F., Shah, P. L., de Matos, C., Russell, R. E. K., Donnelly, L., & Barnes, P. J. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200204-298oc · Cited by 333 · see citing works
Serum amyloid A induces IL-8 secretion through a G protein–coupled receptor, FPRL1/LXA4R
He, R., Sang, H., & Ye, R. D. (2003) · Blood · doi:10.1182/blood-2002-05-1431 · Cited by 329 · see citing works
Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers
Willemse, B. W. M., ten Hacken, N. H. T., Rutgers, B., Lesman‐Leegte, I., Postma, D. S., & Timens, W. (2005) · European Respiratory Journal · doi:10.1183/09031936.05.00108904 · Cited by 317 · see citing works
Dufton, N., Hannon, R., Brancaleone, V., Dalli, J., Patel, H., Gray, M., D’Acquisto, F., Buckingham, J. C., Perretti, M., & Flower, R. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903526 · Cited by 298 · see citing works
Infectious Etiology of Acute Exacerbations of Chronic Bronchitis
Sethi, S. (2000) · CHEST Journal · doi:10.1378/chest.117.5_suppl_2.380s · Cited by 297 · see citing works
Cutting Edge: TLR2 Is a Functional Receptor for Acute-Phase Serum Amyloid A
Cheng, N., He, R., Tian, J., Ye, P. P., & Ye, R. D. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.22 · Cited by 284 · see citing works
Serum Amyloid A Is a Biomarker of Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Bozinovski, S., Hutchinson, A., Thompson, M., MacGregor, L., Black, J., Giannakis, E., Karlsson, A.-S., Silvestrini, R., Smallwood, D., Vlahos, R., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200705-678oc · Cited by 260 · see citing works
Self-citationDiminished Lipoxin Biosynthesis in Severe Asthma
Levy, B. D., Bonnans, C., Silverman, E. S., Palmer, L. J., Marigowda, G., & Israel, E. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200410-1413oc · Cited by 250 · see citing works
Self-citationIs serum amyloid A an endogenous TLR4 agonist?
Sandri, S., Rodriguez, D., Gomes, E., Monteiro, H. P., Russo, M., & Campa, A. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0407203 · Cited by 188 · see citing works
Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound
Vachier, I., Bonnans, C., Chavis, C., Farce, M., Godard, P., Bousquet, J., & Chanez, P. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.09.038 · Cited by 154 · see citing works
O’Hara, R., Murphy, E. P., Whitehead, A. S., FitzGerald, O., & Bresnihan, B. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20301 · Cited by 149 · see citing works
Mullan, R. H., Bresnihan, B., Golden‐Mason, L., Markham, T., O’Hara, R., FitzGerald, O., Veale, D. J., & Fearon, U. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21518 · Cited by 142 · see citing works
Association Between Serum Amyloid A Proteins and Coronary Artery Disease
Fyfe, A. I., Rothenberg, L. S., deBeer, F. C., Cantor, R. M., Rotter, J. I., & Lusis, A. J. (1997) · Circulation · doi:10.1161/01.cir.96.9.2914 · Cited by 137 · see citing works
Kebir, D. E., József, L., Khreiss, T., Pan, W., Petasis, N. A., Serhan, C. N., & Filep, J. G. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.1.616 · Cited by 136 · see citing works
Lipoxin A4 Regulates Bronchial Epithelial Cell Responses to Acid Injury
Bonnans, C., Fukunaga, K., Levy, M. A., & Levy, B. D. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.051056 · Cited by 129 · see citing works
Self-citationNonexpression of the Human Serum Amyloid A Three (SAA3) Gene
Kluve‐Beckerman, B., Drumm, M. L., & Benson, M. D. (1991) · DNA and Cell Biology · doi:10.1089/dna.1991.10.651 · Cited by 125 · see citing works
Levy, B. D., Lukacs, N. W., Berlin, A. A., Schmidt, B. A. R., Guilford, W. J., Serhan, C. N., & Parkinson, J. F. (2007) · The FASEB Journal · doi:10.1096/fj.07-8653com · Cited by 110 · see citing works
Self-citationMorris, T., Stables, M. J., Colville‐Nash, P., Newson, J., Bellingan, G. J., de Souza, P. M., & Gilroy, D. W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000373107 · Cited by 106 · see citing works
Yan, C. H. E. N., Chen, P., Hanaoka, M., Droma, Y., & Kubo, K. (2008) · Respirology · doi:10.1111/j.1440-1843.2008.01365.x · Cited by 105 · see citing works
Endogenous lipid mediators in the resolution of airway inflammation
Haworth, O., & Levy, B. D. (2007) · European Respiratory Journal · doi:10.1183/09031936.00005807 · Cited by 88 · see citing works
Self-citationOkamoto, H., Katagiri, Y., Kiire, A., Momohara, S., & Kamatani, N. (2008) · PubMed · Cited by 61 · see citing works
Thorn, C. F., & Whitehead, A. S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.1.399 · Cited by 59 · see citing works
Marsche, G., Frank, S., Raynes, J. G., Kozarsky, K., Sattler, W., & Malle, E. (2007) · Biochemical Journal · doi:10.1042/bj20061406 · Cited by 53 · see citing works
Thorn, C. F., Lü, Z.-Y., & Whitehead, A. S. (2003) · European Journal of Immunology · doi:10.1002/eji.200323985 · Cited by 51 · see citing works
Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes
Sawmynaden, P., & Perretti, M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.179 · Cited by 48 · see citing works
RAYNAUD'S PHENOMENON IN RHEUMATOID ARTHRITIS
Saraux, A., ALLAIN, J., Guedes, C., Baron, D., Youinou, P., & Goff, P. L. (1996) · Lara D. Veeken · doi:10.1093/rheumatology/35.8.752 · Cited by 46 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators
Serhan, C. N., & Levy, B. D. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97943 · Cited by 1,344 · see citing works
Self-citationSpecialized pro-resolving mediators: endogenous regulators of infection and inflammation
Basil, M. C., & Levy, B. D. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.4 · Cited by 805 · see citing works
Self-citationSack, G. H. (2018) · Molecular Medicine · doi:10.1186/s10020-018-0047-0 · Cited by 507 · see citing works
Cellular and Molecular Mechanisms of Chronic Obstructive Pulmonary Disease
Barnes, P. J. (2013) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2013.10.004 · Cited by 491 · see citing works
Cooray, S. N., Gobbetti, T., Montero‐Melendez, T., McArthur, S., Thompson, D., Clark, A. J. L., Flower, R. J., & Perretti, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308253110 · Cited by 301 · see citing works
Resolution of Acute Inflammation in the Lung
Levy, B. D., & Serhan, C. N. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170408 · Cited by 302 · see citing works
Self-citationEl Kebir, D., Gjorstrup, P., & Filep, J. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206641109 · Cited by 289 · see citing works
DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation
Duvall, M. G., & Levy, B. D. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.11.001 · Cited by 287 · see citing works
Self-citationThe Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition
He, H.-Q., & Ye, R. D. (2017) · Molecules · doi:10.3390/molecules22030455 · Cited by 283 · see citing works
Buck, M. D., Gouwy, M., Wang, J., Snick, J. V., Opdenakker, G., Struyf, S., & Damme, J. V. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160418114600 · Cited by 248 · see citing works
Role of alveolar macrophages in chronic obstructive pulmonary disease
Vlahos, R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00435 · Cited by 246 · see citing works
Self-citationUpdate on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7
Bäck, M., Powell, W. S., Dahlén, S., Drazen, J. M., Evans, J. F., Serhan, C. N., Shimizu, T., Yokomizo, T., & Rovati, G. E. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12665 · Cited by 217 · see citing works
Lipoxins: nature's way to resolve inflammation
Sharma-Walia, N., & Chandrasekharan, J. A. (2015) · Journal of Inflammation Research · doi:10.2147/jir.s90380 · Cited by 234 · see citing works
Formyl-Peptide Receptors in Infection, Inflammation, and Cancer
Weiß, E., & Kretschmer, D. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.08.005 · Cited by 189 · see citing works
Animal models of chronic obstructive pulmonary disease
Fricker, M., Deane, A., & Hansbro, P. M. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.909805 · Cited by 169 · see citing works
Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists
Cattaneo, F., Parisi, M., & Ammendola, R. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14047193 · Cited by 168 · see citing works
The cytokine-serum amyloid A-chemokine network
Buck, M. D., Gouwy, M., Wang, J. M., Snick, J. V., Proost, P., Struyf, S., & Damme, J. V. (2015) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.12.010 · Cited by 157 · see citing works
Fang, X., Abbott, J. A., Cheng, L., Colby, J. K., Lee, J. W., Levy, B. D., & Matthay, M. A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500244 · Cited by 153 · see citing works
Self-citationSerum Amyloid A (SAA) Proteins
Sack, G. H. (2020) · Subcellular Biochemistry · doi:10.1007/978-3-030-41769-7_17 · Cited by 149 · see citing works
COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link
Bozinovski, S., Vlahos, R., Anthony, D., McQualter, J. L., Anderson, G. P., Irving, L. B., & Steinfort, D. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13198 · Cited by 135 · see citing works
Self-citationRegulation of inflammation by members of the formyl-peptide receptor family
Chen, K., Bao, Z., Gong, W., Tang, P., Yoshimura, T., & Wang, J. M. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.06.012 · Cited by 135 · see citing works
Park, J., Langmead, C. J., & Riddy, D. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00075 · Cited by 133 · see citing works
Immune resolution mechanisms in inflammatory arthritis
Perretti, M., Cooper, D., Dalli, J., & Norling, L. V. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.193 · Cited by 126 · see citing works
Targeting Neutrophils for Promoting the Resolution of Inflammation
Filep, J. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.866747 · Cited by 128 · see citing works
Modulation of Neutrophil Apoptosis and the Resolution of Inflammation through β2 Integrins
Kebir, D. E., & Filep, J. G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00060 · Cited by 121 · see citing works
Exhaled breath condensate eicosanoid levels associate with asthma and its severity
Kazani, S. D., Planagumà, A., Ono, E., Bonini, M., Zahid, M., Marigowda, G., Wechsler, M. E., Levy, B. D., & Israel, E. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.01.058 · Cited by 105 · see citing works
Self-citationDalli, J., Consalvo, A. P., Ray, V., Filippo, C. D., D’Amico, M., Mehta, N., & Perretti, M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203000 · Cited by 105 · see citing works
RAGE: a new frontier in chronic airways disease
Sukkar, M. B., Ullah, M. A., Gan, W. J., Wark, P. A. B., Chung, K. F., Hughes, J. M., Armour, C. L., & Phipps, S. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01984.x · Cited by 98 · see citing works
Self-citationAcute-Phase Serum Amyloid A in Osteoarthritis: Regulatory Mechanism and Proinflammatory Properties
de Seny, D., Cobraiville, G., Charlier, E., Neuville, S., Esser, N., Malaise, D., Malaise, O., Calvo, F. Q., Relić, B., & Malaise, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066769 · Cited by 91 · see citing works
Laucho-Contreras, M. E., Polverino, F., Tesfaigzi, Y., Pilon, A. L., Celli, B. R., & Owen, C. A. (2016) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1139084 · Cited by 90 · see citing works
Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation
Kebir, D. E., & Filep, J. G. (2013) · Cells · doi:10.3390/cells2020330 · Cited by 89 · see citing works
Specialized Proresolving Mediators in Innate and Adaptive Immune Responses in Airway Diseases
Krishnamoorthy, N., Abdulnour, R.-E. E., Walker, K. H., Engstrom, B. D., & Levy, B. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00026.2017 · Cited by 84 · see citing works
Self-citationTylek, K., Trojan, E., Regulska, M., Lacivita, E., Leopoldo, M., & Basta‐Kaim, A. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00271-x · Cited by 83 · see citing works
Targońska‐Stępniak, B., & Majdan, M. (2014) · Mediators of Inflammation · doi:10.1155/2014/793628 · Cited by 82 · see citing works
Resolvin D1 Reduces Emphysema and Chronic Inflammation
Hsiao, H.-M., Thatcher, T. H., Colas, R. A., Serhan, C. N., Phipps, R. P., & Sime, P. J. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.08.008 · Cited by 80 · see citing works
Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD
Balgoma, D., Yang, M., Sjödin, M. O. D., Snowden, S. G., Karimi, R., Levänen, B., Merikallio, H., Kaarteenaho, R. L., Palmberg, L., Larsson, K., et al. (2016) · European Respiratory Journal · doi:10.1183/13993003.01080-2015 · Cited by 77 · see citing works
Filep, J. G., & Ariel, A. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00181.2020 · Cited by 75 · see citing works
Therapeutic Potential of Lipoxin A4 in Chronic Inflammation: Focus on Cardiometabolic Disease
Fu, T., Mohan, M., Brennan, E. P., Woodman, O. L., Godson, C., Kantharidis, P., Ritchie, R. H., & Qin, C. X. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00097 · Cited by 76 · see citing works
Pruning of the Pulmonary Vasculature in Asthma. The Severe Asthma Research Program (SARP) Cohort
Ash, S. Y., Rahaghi, F. N., Come, C. E., Ross, J. C., Colon, A., Cardet, J. C., Dunican, E. M., Bleecker, E. R., Castro, M., Fahy, J. V., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201712-2426oc · Cited by 75 · see citing works
Self-citationAnnexin A1 and resolution of inflammation: tissue repairing properties and signalling signature
Gobbetti, T., & Cooray, S. N. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0200 · Cited by 72 · see citing works
Haw, T. J., Starkey, M. R., Nair, P. M., Pavlidis, S. P., Liu, G., Nguyen, D. H., Hsu, A., Hanish, I., Kim, R., Collison, A., et al. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.111 · Cited by 70 · see citing works
Self-citationExpression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages
Jumeau, C., Awad, F., Assrawi, E., Cobret, L., Duquesnoy, P., Giurgea, I., Valeyre, D., Grateau, G., Amselem, S., Bernaudin, J., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217005 · Cited by 70 · see citing works
Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease
Tsantikos, E., Lau, M., Castelino, C. M. N., Maxwell, M. J., Passey, S. L., Hansen, M. J., McGregor, N. E., Sims, N. A., Steinfort, D., Irving, L. B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci98224 · Cited by 67 · see citing works
Self-citationWang, H., Anthony, D., Yatmaz, S., Wijburg, O. L. C., Satzke, C., Levy, B. D., Vlahos, R., & Bozinovski, S. (2017) · Clinical Science · doi:10.1042/cs20171006 · Cited by 68 · see citing works
Self-citationSerum Amyloid A Promotes Lung Neutrophilia by Increasing IL-17A Levels in the Mucosa and γδ T Cells
Anthony, D., Seow, H. J., Uddin, M., Thompson, M. A., Dousha, L. F., Vlahos, R., Irving, L. B., Levy, B. D., Anderson, G. P., & Bozinovski, S. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201211-2139oc · Cited by 67 · see citing works
Self-citationS100A8 Induces IL-10 and Protects against Acute Lung Injury
Hiroshima, Y., Hsu, K., Tedla, N. T., Chung, Y. M., Chow, S., Herbert, C. A., & Geczy, C. L. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302556 · Cited by 63 · see citing works
Erickson, M. A., Jude, J. A., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W. F., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201600857rrr · Cited by 62 · see citing works
Levy, B. D. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00390 · Cited by 60 · see citing works
Self-citationPulmonary biomarkers in COPD exacerbations: a systematic review
Koutsokera, A., Κostikas, Κ., Nicod, L. P., & Fitting, J.-W. (2013) · Respiratory Research · doi:10.1186/1465-9921-14-111 · Cited by 60 · see citing works
Hsiao, H.-M., Thatcher, T. H., Levy, E. P., Fulton, R. A., Owens, K. M., Phipps, R. P., & Sime, P. J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400313 · Cited by 57 · see citing works
Duvall, M. G., Brüggemann, T. R., & Levy, B. D. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.003 · Cited by 57 · see citing works
Self-citationAnthony, D., McQualter, J. L., Bishara, M., Lim, E. X., Yatmaz, S., Seow, H. J., Hansen, M. J., Thompson, M. A., Hamilton, J. A., Irving, L. B., et al. (2014) · The FASEB Journal · doi:10.1096/fj.14-250332 · Cited by 56 · see citing works
Self-citationTreating neutrophilic inflammation in COPD by targeting ALX/FPR2 resolution pathways
Bozinovski, S., Anthony, D., Anderson, G. P., Irving, L. B., Levy, B. D., & Vlahos, R. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.007 · Cited by 55 · see citing works
Self-citationBiasing the lipoxin A 4 /formyl peptide receptor 2 pushes inflammatory resolution
Filep, J. G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317798110 · Cited by 55 · see citing works
Resolving Viral-Induced Secondary Bacterial Infection in COPD: A Concise Review
Wang, H., Anthony, D., Selemidis, S., Vlahos, R., & Bozinovski, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02345 · Cited by 54 · see citing works
Self-citationFormyl peptide receptors in the mucosal immune system
Jeong, Y. S., & Bae, Y. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00518-2 · Cited by 51 · see citing works
Serum amyloid A: A potential biomarker of lung disorders
Vietri, L., Fui, A., Bergantini, L., d’Alessandro, M., Cameli, P., Sestini, P., Rottoli, P., & Bargagli, E. (2019) · Respiratory Investigation · doi:10.1016/j.resinv.2019.09.005 · Cited by 50 · see citing works
Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4
Hirai, K., Furusho, H., Kawashima, N., Xu, S., de Beer, M. C., Battaglino, R. A., Dyke, T. E. V., Stashenko, P., & Sasaki, H. (2018) · Journal of Dental Research · doi:10.1177/0022034518796456 · Cited by 48 · see citing works
Lee, C. H. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-020-01299-y · Cited by 48 · see citing works
Tsai, Y., Yang, S., & Hwang, T. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2016.1216546 · Cited by 45 · see citing works
Kotlyarov, S. N., & Котлярова, А. А. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147634 · Cited by 49 · see citing works
Serum Amyloid A Is a Marker for Pulmonary Involvement in Systemic Sclerosis
Lakota, K., Carns, M. A., Podlusky, S., Mrak‐Poljšak, K., Hinchcliff, M., Lee, J. J., Tomšič, M., Sodin‐Šemrl, S., & Varga, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0110820 · Cited by 44 · see citing works
Effects of Smoking on Inflammatory-Related Cytokine Levels in Human Serum
Wang, H., Chen, H., Fu, Y., Liu, M., Zhang, J., Han, S., Tian, Y., Hou, H., & Hu, Q. (2022) · Molecules · doi:10.3390/molecules27123715 · Cited by 47 · see citing works
Awji, E. G., Chand, H. S., Bruse, S., Smith, K. R., Colby, J. K., Mebratu, Y. A., Levy, B. D., & Tesfaigzi, Y. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2014-0142oc · Cited by 43 · see citing works
Self-citationInsuela, D. B. R., Ferrero, M. R., Coutinho, D. D. S., Martins, M. A., & Carvalho, V. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580598 · Cited by 43 · see citing works
Duvall, M. G., Krishnamoorthy, N., & Levy, B. D. (2018) · Allergology International · doi:10.1016/j.alit.2018.11.006 · Cited by 42 · see citing works
Self-citationSerum Amyloid A1: A Biomarker for Neutrophilic Airway Inflammation in Adult Asthmatic Patients
Cao, T. B. T., Quoc, Q. L., Choi, Y., Yang, E., Trinh, H. K. T., Shin, Y. S., & Park, H. (2022) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2022.14.1.40 · Cited by 42 · see citing works
Targeting pro-resolution pathways to combat chronic inflammation in COPD.
Bozinovski, S., Anthony, D., & Vlahos, R. (2014) · PubMed Central · doi:10.3978/j.issn.2072-1439.2014.08.08 · Cited by 40 · see citing works
Self-citationJiang, T., Shi, L., Wei, L., Li, X., Yang, S., Wang, C., Liu, C., Chen, Z., Tu, H., Li, Z., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173304 · Cited by 39 · see citing works
Passey, S. L., Bozinovski, S., Vlahos, R., Anderson, G. P., & Hansen, M. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146882 · Cited by 37 · see citing works
Self-citationSmole, U., Kratzer, B., & Pickl, W. F. (2020) · European Journal of Immunology · doi:10.1002/eji.201847811 · Cited by 37 · see citing works
ALX receptor ligands define a biochemical endotype for severe asthma
Ricklefs, I., Barkas, I., Duvall, M. G., Cernadas, M., Grossman, N. L., Israel, E., Bleecker, E. R., Castro, M., ERZURUM, S. C., Fahy, J. V., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.93534 · Cited by 37 · see citing works
Self-citationManaging Older Patients with Coexistent Asthma and Chronic Obstructive Pulmonary Disease
McDonald, V. M., Higgins, I., & Gibson, P. G. (2012) · Drugs & Aging · doi:10.1007/s40266-012-0042-z · Cited by 37 · see citing works
Decoding mechanisms and protein markers in lung-brain axis
Huang, S., Zhou, Y., Ji, H., Zhang, T., Liu, S., Ma, L., Deng, D., Ding, Y., Han, L., Shu, S., et al. (2025) · Respiratory Research · doi:10.1186/s12931-025-03272-z · Cited by 36 · see citing works
Zhou, Y., Chen, Y., Zhong, X., Xia, H., Zhao, M., Zhao, M., Xu, L., Guo, X., You, C., Jiang, C., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1060441 · Cited by 36 · see citing works
Airway epithelial regulation of allergic sensitization in asthma
Poynter, M. E. (2012) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2012.04.005 · Cited by 35 · see citing works
Characterization of the Oligomerization and Aggregation of Human Serum Amyloid A
Patke, S., Srinivasan, S., Maheshwari, R., Srivastava, S. K., Aguilera, J. J., Colón, W., & Kane, R. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064974 · Cited by 35 · see citing works
ALX receptor ligands define a biochemical endotype for severe asthma
Ricklefs, I., Barkas, I., Duvall, M. G., Cernadas, M., Grossman, N. L., Israel, E., Bleecker, E. R., Castro, M., ERZURUM, S. C., Fahy, J. V., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120932 · Cited by 34 · see citing works
Self-citationTargeting formyl peptide receptors to facilitate the resolution of inflammation
Filep, J. G., Sekheri, M., & Kebir, D. E. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.06.025 · Cited by 35 · see citing works
Role of arachidonic acid lipoxygenase pathway in Asthma
Luo, Y., Jin, M., Lou, L., Song, Y., Li, C., Li, X., Zhou, M., & Cai, C. (2021) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2021.106609 · Cited by 33 · see citing works
Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis
Lin, N., Shay, J. E. S., Xie, H. J., Lee, D. S. M., Skuli, N., Tang, Q., Zhou, Z., Azzam, A., Meng, H., Wang, H., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02565 · Cited by 30 · see citing works
Porsbjerg, C. M., Rupani, H., Brannan, J. D., Ueki, S., Nawijn, M. C., Erjefalt, J. S., Chanez, P., Anderson, G. P., & Pavord, I. D. (2025) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(25)00299-1 · Cited by 31 · see citing works
Self-citationRole of Apoptotic Cell Clearance in Pneumonia and Inflammatory Lung Disease
Zheng, D. J., Taka, M. A., & Heit, B. (2021) · Pathogens · doi:10.3390/pathogens10020134 · Cited by 32 · see citing works
Moreno, G., Errea, A. J., Maele, L. V., Roberts, R., Léger, H., Sirard, J., Benecke, A., Rumbo, M., & Hozbor, D. F. (2013) · Microbes and Infection · doi:10.1016/j.micinf.2013.06.010 · Cited by 30 · see citing works
Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility
Signorini, C., Moretti, E., Noto, D., Micheli, L., Ponchia, R., & Collodel, G. (2022) · Antioxidants · doi:10.3390/antiox11010107 · Cited by 32 · see citing works
Hansen, M. J., Chan, S. P. J., Langenbach, S. Y., Dousha, L. F., Jones, J. E. C., Yatmaz, S., Seow, H. J., Vlahos, R., Anderson, G. P., & Bozinovski, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113180 · Cited by 30 · see citing works
Self-citationLópez-Campos, J. L., Calero, C., Rojano, B., López-Porras, M., Coronilla, J. S., Blanco, A., Sánchez‐López, V., Tobar, D., Montes‐Worboys, A., & Arellano, E. (2013) · International Journal of Medical Sciences · doi:10.7150/ijms.6152 · Cited by 30 · see citing works
Zheng, H., Li, H., Zhang, J., Fan, H., Jia, L., Ma, W., Ma, S., Wang, S., You, H., Yin, Z., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010626 · Cited by 29 · see citing works
Ryu, M. H., Afshar, T., Li, H., Wooding, D. J., Orach, J., Zhou, J. S., Murphy, S., Lau, K. S. K., Schwartz, C., Yuen, A. C. Y., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202104-1079oc · Cited by 29 · see citing works
Zhang, Y., Chen, X., Hu, Y., Du, S.-S., Shen, L., He, Y., Zhang, Y., Zhang, X., Li, H., & Yung, R. (2013) · Respiratory Research · doi:10.1186/1465-9921-14-18 · Cited by 29 · see citing works
Regulation of inflammation by lipid mediators in oral diseases
Sommakia, S., & Baker, O. J. (2016) · Oral Diseases · doi:10.1111/odi.12544 · Cited by 29 · see citing works
Quenching the fires: Pro-resolving mediators, air pollution, and smoking
Thatcher, T. H., Woeller, C. F., McCarthy, C. E., & Sime, P. J. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.001 · Cited by 28 · see citing works
Balta, M. G., Papathanasiou, E., & CHRISTOPOULOS, P. F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.632238 · Cited by 28 · see citing works
Wang, H., Blackall, M., Sominsky, L., Spencer, S. J., Vlahos, R., Churchill, M. J., & Bozinovski, S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1234-1 · Cited by 29 · see citing works
Self-citationSpecialized proresolving mediators in infection and lung injury
Sandhaus, S., & Swick, A. G. (2020) · BioFactors · doi:10.1002/biof.1691 · Cited by 26 · see citing works
Chen, Y., Lin, M., Lee, C., Liu, S., Wang, C., Fang, W., Chao, T.-Y., Wu, C., Wei, Y., Chang, H., et al. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1435-5 · Cited by 26 · see citing works
Kang, G.-J., Kim, E. J., & Lee, C. H. (2020) · Antioxidants · doi:10.3390/antiox9121259 · Cited by 24 · see citing works
An investigation of the resolution of inflammation (catabasis) in COPD
Noguera, A., Gómez, C., Faner, R., Cosío, B. G., González‐Périz, A., Clària, J., Carvajal, Á. F., & Agustí, A. G. N. (2012) · Respiratory Research · doi:10.1186/1465-9921-13-101 · Cited by 24 · see citing works
Lokwani, R., Wark, P. A. B., Baines, K. J., Barker, D., & Simpson, J. L. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-024330 · Cited by 24 · see citing works
Self-citationLipoxin A4 improves cardiac remodeling and function in diabetes-associated cardiac dysfunction
Fu, T., Mohan, M., Bose, M., Brennan, E. P., Kiriazis, H., Deo, M., Nowell, C. J., Godson, C., Cooper, M. E., Zhao, P., et al. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02501-x · Cited by 23 · see citing works
- Authors
- Bozinovski, S., Uddin, M., Vlahos, R., Thompson, M., McQualter, J. L., Merritt, A.-S., Wark, P. A. B., Hutchinson, A., Irving, L. B., Levy, B. D., & Anderson, G. P.
- Affiliations
- The University of Melbourne (AU)
- Brigham and Women's Hospital (US)
- Department of Pharmacology, and
- The Royal Melbourne Hospital (AU)
- John Hunter Hospital (AU)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-01-03
- Volume
- 109
- Issue
- 3
- Pages
- 935-940
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3271884
- OpenAlex
- W1969944763
- Cited by
- 163
- References
- 35
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 4 · 2023: 8 · 2022: 11 · 2021: 10 · 2020: 14 · 2019: 9 · 2018: 16 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 12 · 2013: 21 · 2012: 7
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL090927, HL-68669, P50HL107166, HL090927, R01HL068669)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Keywords
- serum amyloid A, lipoxin A4, chronic obstructive pulmonary disease, glucocorticoid resistance, lung inflammation, neutrophil recruitment, airway epithelial cells, interleukin-8, neutrophil elastase, acute exacerbation, lung macrophages, bronchoalveolar lavage fluid
- MeSH terms
- Serum Amyloid A Protein, Animals, Bronchoalveolar Lavage Fluid, Epithelial Cells, Epithelium, Glucocorticoids, Humans, Lung, Macrophages, Mucous Membrane, Neutrophils, Pneumonia, Interleukin-8, Neutrophil Activation, Pulmonary Disease, Chronic Obstructive, Receptors, Formyl Peptide, Lipoxins, Receptors, Lipoxin, Mice
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
