Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response
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The local production of proinflammatory cytokines mediates the host response to inflammation, infection, and injury, whereas an overexpression of these mediators can injure or kill the host. Recently, we identified a class of multivalent guanylhydrazone compounds that are effective inhibitors of proinflammatory cytokine synthesis in monocytes/macrophages. The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection. Here, we addressed the hypothesis that spermine might counterregulate the innate immune response by downregulating the synthesis of potentially injurious cytokines. When spermine was added to cultures of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, MIP-1alpha, and MIP-1beta. The inhibition of cytokine synthesis was specific and reversible, with significant inhibition of TNF synthesis occurring even when spermine was added after LPS. The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity. Local administration of spermine in vivo protected mice against the development of acute footpad inflammation induced by carrageenan. These results identify a distinct molecular counterregulatory role for spermine in downregulating the monocyte proinflammatory cytokine response.
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Extraneous spermine is taken up by monocytes and macrophages and selectively inhibits LPS-induced expression of pro-inflammatory cytokines.
“Extraneous spermine is taken up by monocytes and macrophages and selectively inhibits the LPS-induced expression of pro-inflammatory cytokines (M. Zhang et al., 1999; 1997).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as M. Zhang et al., 1997
Spermine administration has protective anti-inflammatory effects in mouse models of localized and systemic inflammation.
“spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (Steege et al., 1999; M. Zhang et al., 1997; S. Zhu et al., 2009).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as M. Zhang et al., 1997
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Cites
Biologic basis for interleukin-1 in disease.
Dinarello, C. (1996) · Blood · doi:10.1182/blood.v87.6.2095.bloodjournal8762095 · Cited by 3,380 · see citing works
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549 · see citing works
Self-citationAnti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A. (1987) · Nature · doi:10.1038/330662a0 · Cited by 2,448 · see citing works
Self-citationPfeffer, K., Matsuyama, T., Kündig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P. S., Krönke, M., & Mak, T. W. (1993) · Cell · doi:10.1016/0092-8674(93)90134-c · Cited by 1,677 · see citing works
Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
Scheinman, R. I., Cogswell, P. C., Lofquist, A. K., & Baldwin, A. S. (1995) · Science · doi:10.1126/science.270.5234.283 · Cited by 1,676 · see citing works
Control of Cachectin (Tumor Necrosis Factor) Synthesis: Mechanisms of Endotoxin Resistance
Beutler, B., Krochin, N., Milsark, I. W., Luedke, C. E., & Cerami, A. (1986) · Science · doi:10.1126/science.3754653 · Cited by 1,268 · see citing works
Self-citationSampaio, E. P., Sarno, E. N., Gallily, R., Cohn, Z. A., & Kaplan, G. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.699 · Cited by 1,191 · see citing works
Deactivation of macrophages by transforming growth factor-β
Tsunawaki, S., Sporn, M. B., Ding, A. H., & Nathan, C. (1988) · Nature · doi:10.1038/334260a0 · Cited by 862 · see citing works
Gerard, C. M., Bruyns, C., Marchant, A., Abramowicz, D., Vandenabeele, P., Delvaux, A., Fiers, W., Goldman, M., & Velu, T. J. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.2.547 · Cited by 786 · see citing works
Fong, Y., Tracey, K. J., Moldawer, L. L., HESSE, D. G., Manogue, K., Kenney, J. S., Lee, A. T., Kuo, G. C., ALLISON, A. C., & Lowry, S. F. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.5.1627 · Cited by 640 · see citing works
Self-citationRomero, R. J., González, R., Sepúlveda, W., Brandt, F., Ramírez, M., Sorokin, Y., Mazor, M., Treadwell, M. C., & Cotton, D. B. (1992) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(12)80043-3 · Cited by 598 · see citing works
Wolpe, S. D., Davatelis, G., Sherry, B. A., Beutler, B., HESSE, D. G., Nguyen, H. T., Moldawer, L. L., Nathan, C. F., Lowry, S. F., & Cerami, A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.2.570 · Cited by 571 · see citing works
Self-citationDing, A. H., Nathan, C., Graycar, J. L., Derynck, R., Stuehr, D. J., & Srimal, S. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.3.940 · Cited by 500 · see citing works
Randow, F., Syrbe, U., Meisel, C., Krausch, D., Zuckermann, H., Platzer, C., & Volk, H. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.5.1887 · Cited by 446 · see citing works
Romero, R. J., Manogue, K. R., Mitchell, M. D., Wu, Y., Enrique Oyarzún, E., Hobbins, J. C., & Cerami, A. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90515-2 · Cited by 426 · see citing works
Self-citationIdentification and characterization of macrophage inflammatory protein 2.
Wolpe, S. D., Sherry, B. A., Juers, D. H., Davatelis, G., Yurt, R. W., & Cerami, A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.2.612 · Cited by 425 · see citing works
Self-citationOswald, I. P., Wynn, T. A., Sher, A., & James, S. L. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.18.8676 · Cited by 353 · see citing works
Martínez Martínez, L. (1990) · PubMed · Cited by 334 · see citing works
Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis.
Titus, R. G., Sherry, B. A., & Cerami, A. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.6.2097 · Cited by 246 · see citing works
Self-citationCytokines in Health and Disease
Kunkel, S. L., & Remick, D. G. (1992) · Medical Entomology and Zoology · Cited by 197 · see citing works
Donnelly, R. P., Freeman, S., & Hayes, M. P. (1995) · Journal of Immunology · doi:10.4049/jimmunol.155.3.1420 · Cited by 178 · see citing works
Sherry, B. A., Alava, G., Tracey, K. J., Martiney, J. A., Cerami, A., & Slater, A. F. G. (1995) · PubMed · Cited by 158 · see citing works
Self-citationInteractive effects of the tumor necrosis factor promoter and 3’-untranslated regions
Han, J., Huez, G., & Beutler, B. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.6.1843 · Cited by 148 · see citing works
Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone.
Bianchi, M., Bloom, O., Raabe, T. D., Cohen, P. S., Chesney, J. A., Sherry, B. A., Schmidtmayerova, H., Calandra, T., Zhang, X., Bukrinsky, M., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.927 · Cited by 127 · see citing works
Self-citationDing, A. H., Sánchez, E., Srimal, S., & Nathan, C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84941-4 · Cited by 125 · see citing works
Control by IFN-gamma and PGE2 of TNF alpha and IL-1 production by human monocytes.
Hart, P. H., Whitty, G. A., Piccoli, D. S., & Hamilton, J. A. (1989) · PubMed Central · Cited by 121 · see citing works
Ianaro, A., O'Donnell, C. A., Rosa, M. D., & Liew, F. Y. (1994) · PubMed Central · Cited by 121 · see citing works
Bianchi, M., Ulrich, P. C., Bloom, O., Meistrell, M. E., Zimmerman, G. A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B. A., et al. (1995) · Molecular Medicine · doi:10.1007/bf03401550 · Cited by 116 · see citing works
Self-citationThe influence of catabolic reactions on polyamine excretion
Seiler, N., Bolkenius, F. N., & Knödgen, B. (1985) · Biochemical Journal · doi:10.1042/bj2250219 · Cited by 109 · see citing works
Interleukin-10 is upregulated in LPS tolerance.
Frankenberger, M., Pechumer, H., & Ziegler-Heitbrock, H. W. L. (1995) · PubMed · Cited by 99 · see citing works
Cohen, P. S., Nakshatri, H., Dennis, J., Caragine, T. A., Bianchi, M., Cerami, A., & Tracey, K. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.3967 · Cited by 95 · see citing works
Self-citationLehmmann, V., Benninghoff, B., & Dröge, W. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.2.587 · Cited by 81 · see citing works
Sinha, B. N. M., Semmler, J., Eisenhut, T., Eigler, A., & Endres, S. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250125 · Cited by 80 · see citing works
Luedke, C. E., & Cerami, A. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114829 · Cited by 75 · see citing works
Self-citationSzabó, C., Southan, G. J., Wood, E. G., Thiemermann, C., & Vane, J. R. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb13078.x · Cited by 75 · see citing works
THE EFFECT OF SPERMINE ON TUBERCLE BACILLI
Hirsch, J. G., & Dubos, R. J. (1952) · The Journal of Experimental Medicine · doi:10.1084/jem.95.2.191 · Cited by 74 · see citing works
Baydoun, A. R., Bogle, R., Pearson, J. D., & Mann, G. E. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb13099.x · Cited by 73 · see citing works
Polyamine oxidation, programmed cell death, and regulation of melanoma in the murine embryonic limb.
Parchment, R. E., & Pierce, G. B. (1989) · PubMed · Cited by 64 · see citing works
The natural polyamines and the immune system
Seiler, N., & Atanassov, C. L. (1994) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7156-3_4 · Cited by 62 · see citing works
Determination of polyamine oxidase activities in human tissues
Suzuki, O., Matsumoto, T., & Katsumata, Y. (1984) · Cellular and Molecular Life Sciences · doi:10.1007/bf01951981 · Cited by 50 · see citing works
[28] Carrageenan foot edema test
Otterness, I. G., & Moore, P. F. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)62086-6 · Cited by 49 · see citing works
Caccia, S., Anelli, M., Codegoni, A. M., Fracasso, C., & Garattini, S. K. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13817.x · Cited by 49 · see citing works
High-resolution X-ray Diffraction by Single Crystals of Mixtures of Transfer Ribonucleic Acids
Blake, R. D., Fresco, J. R., & Langridge, R. (1970) · Nature · doi:10.1038/225032a0 · Cited by 48 · see citing works
Evidence linking programmed cell death in the blastocyst to polyamine oxidation
Gramzinski, R. A., Parchment, R. E., & Pierce, G. B. (1990) · Differentiation · doi:10.1111/j.1432-0436.1990.tb00430.x · Cited by 44 · see citing works
HPLC and NMR Investigation of the Serum Amine Oxidase Catalyzed Oxidation of Polyamines.
Houen, G., Bock, K., Jensen, A. L., Weidlein, J., Schnöckel, H., Paulsen, G. B., Nielsen, R. I., Olsen, C. E., Pedersen, C., & Stidsen, C. E. (1994) · Acta chemica Scandinavica/Acta chemica Scandinavica. B, Organic chemistry and biochemistry/Acta chemica Scandinavica. A, Physical and inorganic chemistry/Acta chemica Scandinavica. Series B. Organic chemistry and biochemistry/Acta chemica Scandinavica. Series A, Physical and inorganic chemistry · doi:10.3891/acta.chem.scand.48-0052 · Cited by 41 · see citing works
Polyamine oxidation down-regulates IL-2 production by human peripheral blood mononuclear cells.
Flescher, E., Bowlin, T. L., & Talal, N. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.142.3.907 · Cited by 41 · see citing works
Effect of Pregnancy Sera on Isolated Lysosomes
Hempel, K., FERNANDEZ, L. A., & Persellin, R. H. (1970) · Nature · doi:10.1038/225955a0 · Cited by 40 · see citing works
PRODUCTION OF AN ANTI‐INFLAMMATORY SUBSTANCE AT A SITE OF INFLAMMATION
Robinson, B. V., & Robson, J. M. (1964) · British Journal of Pharmacology and Chemotherapy · doi:10.1111/j.1476-5381.1964.tb01598.x · Cited by 32 · see citing works
Inhibition of human neutrophil locomotion by the polyamine oxidase-polyamine system.
Ferrante, A. (1985) · PubMed · Cited by 30 · see citing works
Gonzalez, J. C., Johnson, D., Morrison, D. C., Freudenberg, M. A., Galanos, C., & Silverstein, R. (1993) · Infection and Immunity · doi:10.1128/iai.61.3.970-974.1993 · Cited by 30 · see citing works
Polyamines and Prostatic Carcinoma: Clinical and Therapeutic Implications
Cipolla, B. G., Guillé, F., Moulinoux, J.-P., Quémener, V., Staerman, F., Corbel, L., & Lobel, B. (1993) · European Urology · doi:10.1159/000474279 · Cited by 30 · see citing works
Quan, C. P., Roux, C., Pillot, J., & Bouvet, J. (1990) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.1990.tb01033.x · Cited by 27 · see citing works
Lysosome stabilization by adjuvant arthritis serum
Persellin, R. H. (1972) · Arthritis & Rheumatism · doi:10.1002/art.1780150203 · Cited by 26 · see citing works
Recovery of an anti-inflammatory fraction from inflammatory exudate.
Th, R. (1956) · PubMed · Cited by 26 · see citing works
Southan, G. J., Szabó, C., & Thiemermann, C. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2374 · Cited by 25 · see citing works
Inhibitors of polyamine biosynthesis block tumor necrosis factor-induced activation of macrophages.
Kaczmarek, L., Kaminska, B., Messina, L., Spampinato, G., Arcidiacono, A. A., Malaguarnera, L., & Messina, A. (1992) · PubMed · Cited by 22 · see citing works
Polyamine transport regulation by calcium and calmodulin: Role of Ca2+‐ATPase
Khanp, N. A., Sezan, A., Quémener, V., & Moulinoux, J.-P. (1993) · Journal of Cellular Physiology · doi:10.1002/jcp.1041570308 · Cited by 18 · see citing works
Relationship between Tissue Polyamine Levels and Malignancy in Primary Brain Tumors
Kurihara, H., Matsuzaki, S., Yamazaki, H., Tsukahara, T., & Tamura, M. (1993) · Neurosurgery · doi:10.1227/00006123-199303000-00006 · Cited by 15 · see citing works
Morgan, D. M. L. (1987) · PubMed · Cited by 15 · see citing works
Polyamine transport in human promyelocytic leukemia cells and polymorphonuclear leukocytes
Walters, J. D., & Wojcik, M. S. (1994) · Leukemia Research · doi:10.1016/0145-2126(94)90070-1 · Cited by 14 · see citing works
The control of rheumatic disease by endogenous protein
Lewis, D. A., Capstick, R. B., & Best, R. (1976) · Biochemical Pharmacology · doi:10.1016/0006-2952(76)90118-0 · Cited by 13 · see citing works
Flagged first, then by citations
4 of the 65 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775 · see citing works
Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages
Rath, M., ller, I. M. ⁄., Kropf, P., Closs, E. I., & Munder, M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00532 · Cited by 1,271 · see citing works
Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
“Indeed, spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (ter Steege et al., 1999; Zhang et al., 1997; Zhu et al., 2009).”
BackgroundMunder, M., Eichmann, K., & Modolell, M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.11.5347 · Cited by 647 · see citing works
Th1/Th2-Regulated Expression of Arginase Isoforms in Murine Macrophages and Dendritic Cells
Munder, M., Eichmann, K., Morán, J. M., Centeno, F., Soler, G., & Modolell, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3771 · Cited by 561 · see citing works
HMGB1 as a Late Mediator of Lethal Systemic Inflammation
Wang, H., Yang, H., Czura, C. J., Sama, A. E., & Tracey, K. J. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.10.2106117 · Cited by 490 · see citing works
Self-citationSuppression of T-cell functions by human granulocyte arginase
Munder, M. (2006) · Blood · doi:10.1182/blood-2006-11-010389 · Cited by 417 · see citing works
Fetuin-A Regulation of Calcified Matrix Metabolism
Jahnen‐Dechent, W., Heiss, A., Schäfer, C., & Ketteler, M. (2011) · Circulation Research · doi:10.1161/circresaha.110.234260 · Cited by 386 · see citing works
Bifidobacterium mechanisms of immune modulation and tolerance
Gavzy, S. J., Kensiski, A., Lee, Z. L., Mongodin, E. F., Ma, B., & Bromberg, J. S. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2291164 · Cited by 375 · see citing works
IFN-γ Induces High Mobility Group Box 1 Protein Release Partly Through a TNF-Dependent Mechanism
Rendon-Mitchell, B., Ochani, M., Li, J., Han, J., Wang, H., Yang, H., Susarla, S. M., Czura, C. J., Mitchell, R. A., Chen, G., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3890 · Cited by 337 · see citing works
Self-citationImpact of intestinal microbiota on intestinal luminal metabolome
Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Kurihara, S., Sawaki, E., Koga, Y., & Benno, Y. (2012) · Scientific Reports · doi:10.1038/srep00233 · Cited by 334 · see citing works
Haskó, G., Kuhel, D. G., Nemeth, Z. H., Mabley, J. G., Stachlewitz, R. F., Virág, L., Lohinai, Z. M., Southan, G. J., Salzman, A. L., & Szabó, C. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.1013 · Cited by 333 · see citing works
Mondanelli, G., Bianchi, R., Pallotta, M. T., Orabona, C., Albini, E., Iacono, A., Belladonna, M. L., Vacca, C., Fallarino, F., Macchiarulo, A., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.005 · Cited by 335 · see citing works
Control of immune response by amino acid metabolism
Grohmann, U., & Bronte, V. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00915.x · Cited by 311 · see citing works
Lee, S. M., Yune, T. Y., Kim, S. J., Park, D. W., Lee, Y. K., Kim, Y. C., Oh, Y. J., Markelonis, G. J., & Oh, T. H. (2003) · Journal of Neurotrauma · doi:10.1089/089771503770195867 · Cited by 305 · see citing works
Nitric Oxide in Inflammatory Bowel Disease
Cross, R. K., & Wilson, K. T. (2003) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200305000-00006 · Cited by 303 · see citing works
Kropf, P., Fuentes, J. M., Fähnrich, E., Arpa, L., Herath, S., Weber, V., Soler, G., Celada, A., Modolell, M., & Müller, I. (2005) · The FASEB Journal · doi:10.1096/fj.04-3416fje · Cited by 297 · see citing works
Matsumoto, M., Kurihara, S., Kibe, R., Ashida, H., & Benno, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023652 · Cited by 290 · see citing works
Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity
Rodrı́guez, P. C., Ochoa, A. C., & Al-Khami, A. A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00093 · Cited by 287 · see citing works
Kibe, R., Kurihara, S., Sakai, Y., Suzuki, H., Ooga, T., Sawaki, E., Muramatsu, K., Nakamura, A., Yamashita, A., Kitada, Y., et al. (2014) · Scientific Reports · doi:10.1038/srep04548 · Cited by 271 · see citing works
The mechanisms by which polyamines accelerate tumor spread
Soda, K. (2011) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-30-95 · Cited by 271 · see citing works
Self-citationNakamura, A., Kurihara, S., Takahashi, D., Ohashi, W., Nakamura, Y., Kimura, S., Onuki, M., Kume, A., Sasazawa, Y., Furusawa, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22212-1 · Cited by 251 · see citing works
Altered maturation of peripheral blood dendritic cells in patients with breast cancer
Bella, S. D., Gennaro, M., Vaccari, M., Ferraris, C., Nicola, S., Riva, A., Clerici, M., Greco, M., & Villa, M. L. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601243 · Cited by 239 · see citing works
An update in recurrent spontaneous abortion
Pandey, M. K., Rani, R., & Agrawal, S. S. (2005) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-004-0706-y · Cited by 228 · see citing works
Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy
Nenkov, M., Ma, Y., Gaßler, N., & Chen, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126262 · Cited by 222 · see citing works
Polyamine-rich food decreases age-associated pathology and mortality in aged mice
Soda, K., Dobashi, Y., Kano, Y., Tsujinaka, S., & Konishi, F. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.08.013 · Cited by 216 · see citing works
Self-citationHanus, M., Parada‐Venegas, D., Landskron, G., Wielandt, A. M., Hurtado, C., Álvarez, K., Hermoso, M. A., López-Köstner, F., & la Fuente, M. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.612826 · Cited by 201 · see citing works
A wide diversity of bacteria from the human gut produces and degrades biogenic amines
Pugin, B., Barcik, W., Westermann, P., Heider, A., Wawrzyniak, M., Hellings, P., Akdis, C. A., & O’Mahony, L. (2017) · Microbial Ecology in Health and Disease · doi:10.1080/16512235.2017.1353881 · Cited by 198 · see citing works
Nakazato, H., Oku, H., Yamane, S., Tsuruta, Y., & Suzuki, R. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01758-2 · Cited by 187 · see citing works
Chen, G., Li, J., Ochani, M., Rendon-Mitchell, B., Qiang, X., Susarla, S. M., Ulloa, L., Yang, H., Fan, S., Goyert, S. M., et al. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0404242 · Cited by 188 · see citing works
Self-citationThe role of polyamines in the regulation of macrophage polarization and function
Latour, Y. L., Gobert, A. P., & Wilson, K. T. (2019) · Amino Acids · doi:10.1007/s00726-019-02719-0 · Cited by 182 · see citing works
Yarova, P., Stewart, A. L., Sathish, V., Britt, R. D., Thompson, M. A., Lowe, A. P. P., Freeman, M., Aravamudan, B., Kita, H., Brennan, S. C., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa0282 · Cited by 174 · see citing works
Helicobacter pylori Induces Macrophage Apoptosis by Activation of Arginase II
Gobert, A. P., Cheng, Y., Wang, J., Boucher, J., Iyer, R. K., Cederbaum, S. D., Casero, R. A., Newton, J. C., & Wilson, K. T. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.9.4692 · Cited by 173 · see citing works
Genetic risk factor for unexplained recurrent early pregnancy loss
Nelen, W. L. D. M., Steegers, E. A. P., Eskes, T. K. A. B., & Blom, H. J. (1997) · The Lancet · doi:10.1016/s0140-6736(97)24038-9 · Cited by 170 · see citing works
Chaturvedi, R., Cheng, Y., Asim, M., Bussière, F. I., Xu, H., Gobert, A. P., Hacker, A., Casero, R. A., & Wilson, K. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401370200 · Cited by 167 · see citing works
Ochieng, J., & Chaudhuri, G. (2010) · Journal of Health Care for the Poor and Underserved · doi:10.1353/hpu.0.0257 · Cited by 161 · see citing works
Sahin, E., Haubenwallner, S., Kuttke, M., Kollmann, I., Halfmann, A., Dohnal, A. M., Chen, L., Cheng, P. P., Hoesel, B., Einwallner, E., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302167 · Cited by 155 · see citing works
Anti-Inflammatory Role of Fetuin-A in Injury and Infection
Wang, H., & Sama, A. (2012) · Current Molecular Medicine · doi:10.2174/156652412800620039 · Cited by 153 · see citing works
Self-citationLü, B., Wang, C., Wang, M., Li, W., Chen, F., Tracey, K. J., & Wang, H. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.909730 · Cited by 153 · see citing works
Self-citationFetuin (α 2 -HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules
Wang, H., Zhang, M., Bianchi, M., Sherry, B. A., Sama, A. E., & Tracey, K. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14429 · Cited by 146 · see citing works
Self-citationden Bossche, J. V., Lamers, W. H., Köhler, E. S., Geuns, J. M. C., Alhonen, L. I., Uimari, A., Pirnes-Karhu, S., Overmeire, E. V., Morias, Y., Brys, L., et al. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0911453 · Cited by 145 · see citing works
Spermidine and spermine are enriched in whole blood of nona/centenarians
Pucciarelli, S., Moreschini, B., Micozzi, D., De Fronzo, G. S., Carpi, F. M., Polzonetti, V., Vincenzetti, S., Mignini, F., & Napolioni, V. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1349 · Cited by 144 · see citing works
Yeramian, A., Jaular, L. M., Serrat, N., Arpa, L., Soler, C., Bertran, J., McLeod, C., Palacı́n, M., Modolell, M., Lloberas, J., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.10.5918 · Cited by 144 · see citing works
Bussière, F. I., Chaturvedi, R., Cheng, Y., Gobert, A. P., Asim, M., Blumberg, D. R., Xu, H., Kim, P. Y., Hacker, A., Casero, R. A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400498200 · Cited by 144 · see citing works
Regulation of macrophage activation and inflammation by spermine: A new chapter in an old story
Zhang, M., Wang, H., & Tracey, K. J. (2000) · Critical Care Medicine · doi:10.1097/00003246-200004001-00007 · Cited by 142 · see citing works
Self-citationMicrobial Metabolites Determine Host Health and the Status of Some Diseases
Sittipo, P., Shim, J., & Lee, Y. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215296 · Cited by 140 · see citing works
Protective Role of Arginase in a Mouse Model of Colitis
Gobert, A. P., Cheng, Y., Akhtar, M., Mersey, B. D., Blumberg, D. R., Cross, R. K., Chaturvedi, R., Drachenberg, C. B., Boucher, J., Hacker, A., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.2109 · Cited by 122 · see citing works
Patel, N. B., Kreider, T., Urban, J. F., & Gause, W. C. (2008) · International Journal for Parasitology · doi:10.1016/j.ijpara.2008.08.003 · Cited by 117 · see citing works
Bourebaba, L., & Marycz, K. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8122033 · Cited by 123 · see citing works
Zhou, S., Gu, J. H., Liu, R., Song, W., Wang, Q., Shen, H., Dai, Y., Zhou, H., Zhang, F., & Lü, L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00948 · Cited by 120 · see citing works
Ivanova, S., Botchkina, G. I., Al‐Abed, Y., Meistrell, M. E., Batliwalla, F., Dubinsky, J. M., Iadecola, C., Wang, H., Gregersen, P. K., Eaton, J. W., et al. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.2.327 · Cited by 115 · see citing works
Self-citationTherapeutic potential of HMGB1-targeting agents in sepsis
Wang, H., Zhu, S., Zhou, R., Li, W., & Sama, A. E. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000884 · Cited by 113 · see citing works
Self-citationYamamoto, T. M., Hinoi, E., Fujita, H., Iezaki, T., Takahata, Y., Takamori, M., & Yoneda, Y. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01856.x · Cited by 108 · see citing works
Spermine protects mice against lethal sepsis partly by attenuating surrogate inflammatory markers
Zhu, S., Ashok, M., Li, J., Li, W., Yang, H., Wang, P., Tracey, K. J., Sama, A. E., & Wang, H. (2009) · Molecular Medicine · doi:10.2119/molmed.2009.00062 · Cited by 109 · see citing works
Self-citationSoda, K., Kano, Y., Chiba, F., Koizumi, K., & Miyaki, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064357 · Cited by 107 · see citing works
Self-citationHannemann, N., Cao, S., Eriksson, D., Schnelzer, A., Jordan, J., Eberhardt, M., Schleicher, U., Rech, J., Ramming, A., Uebe, S., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci96832 · Cited by 103 · see citing works
Nakamura, A., Ooga, T., & Matsumoto, M. (2018) · Gut Microbes · doi:10.1080/19490976.2018.1494466 · Cited by 100 · see citing works
Magnes, C., Fauland, A., Gander, E., Narath, S. H., Ratzer, M., Eisenberg, T., Madeo, F., Pieber, T. R., & Sinner, F. M. (2014) · Journal of Chromatography A · doi:10.1016/j.chroma.2013.12.061 · Cited by 100 · see citing works
Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway
Czura, C. J., Friedman, S. G., & Tracey, K. J. (2003) · Journal of Endotoxin Research · doi:10.1179/096805103225002755 · Cited by 98 · see citing works
Self-citationActivation of polyamine catabolism in transgenic rats induces acute pancreatitis
Alhonen, L. I., Parkkinen, J. J., Keinänen, T. A., Sinervirta, R., Herzig, K., & Jänne, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140122097 · Cited by 98 · see citing works
Spermine reverses lipopolysaccharide-induced memory deficit in mice
Frühauf, P. K. S., Ineu, R. P., Tomazi, L., Duarte, T., Mello, C. F., & Rubin, M. A. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0220-5 · Cited by 96 · see citing works
Gabandé‐Rodríguez, E., Heras, M. M. G. D. L., & Mittelbrunn, M. (2019) · Cells · doi:10.3390/cells9010082 · Cited by 96 · see citing works
Polyamines and the Intestinal Tract
Seiler, N., & Raul, F. (2007) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360701250016 · Cited by 93 · see citing works
Soulet, D., & Rivest, S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200301097 · Cited by 93 · see citing works
Spermine inhibition of monocyte activation and inflammation
Zhang, M., Borovikova, L. V., Wang, H., Metz, C., & Tracey, K. J. (1999) · Molecular Medicine · doi:10.1007/bf03402072 · Cited by 92 · see citing works
Self-citationPolyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism
Soda, K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103106 · Cited by 91 · see citing works
Self-citationYeramian, A., Jaular, L. M., Arpa, L., Bertran, J., Soler, C., McLeod, C., Modolell, M., Palacı́n, M., Lloberas, J., & Celada, A. (2006) · European Journal of Immunology · doi:10.1002/eji.200535694 · Cited by 91 · see citing works
Arginine and Polyamines Fate in Leishmania Infection
Muxel, S. M., Aoki, J. I., Fernandes, J. C. R., Laranjeira‐Silva, M. F., Zampieri, R. A., Acuña, S. M., Müller, K. E., Vanderlinde, R. H., & Floeter‐Winter, L. M. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02682 · Cited by 88 · see citing works
Choi, B.-S., Martinez-Falero, I. C., Corset, C., Munder, M., Modolell, M., Müller, I., & Kropf, P. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0508310 · Cited by 90 · see citing works
Spermine, a Natural Polyamine, Suppresses LFA-1 Expression on Human Lymphocyte
Soda, K., Kano, Y., Nakamura, T., Kasono, K., Kawakami, M., & Konishi, F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.237 · Cited by 89 · see citing works
Self-citationAmino acids: key sources for immunometabolites and immunotransmitters
Miyajima, M. (2020) · International Immunology · doi:10.1093/intimm/dxaa019 · Cited by 88 · see citing works
Polyamine Catabolism Is Enhanced after Traumatic Brain Injury
Zahedi, K. A., Huttinger, F., Morrison, R. I., Stewart, T. M., Casero, R. A., & Strauss, K. I. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2009.1097 · Cited by 86 · see citing works
Human endothelial cell response to gram-negative lipopolysaccharide assessed with cDNA microarrays
Zhao, B., Bowden, R. A., Stavchansky, S. A., & Bowman, P. D. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.5.c1587 · Cited by 86 · see citing works
Biochemical Features of Beneficial Microbes: Foundations for Therapeutic Microbiology
Engevik, M. A., & Versalovic, J. A. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.bad-0012-2016 · Cited by 85 · see citing works
Soda, K. (2022) · Cells · doi:10.3390/cells11010164 · Cited by 85 · see citing works
Self-citationTargeting Polyamines and Inflammation for Cancer Prevention
Babbar, N., & Gerner, E. W. (2010) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-10858-7_4 · Cited by 82 · see citing works
Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells
McCubbrey, A. L., McManus, S. A., McClendon, J. D., Thomas, S. M., Chatwin, H. B., Reisz, J. A., D’Alessandro, A., Mould, K. J., Bratton, D. L., Henson, P. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110222 · Cited by 81 · see citing works
Inflammation and polyamine catabolism: the good, the bad and the ugly
Babbar, N., Stewart, T. M., & Casero, R. A. (2007) · Biochemical Society Transactions · doi:10.1042/bst0350300 · Cited by 81 · see citing works
Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention
Battaglia, V., Shields, C. E. D., Stewart, T. M., & Casero, R. A. (2013) · Amino Acids · doi:10.1007/s00726-013-1529-6 · Cited by 77 · see citing works
Vitamin D receptor promotes healthy microbial metabolites and microbiome
Chatterjee, I., Lu, R., Zhang, Y., Zhang, J., Dai, Y. D., Xia, Y., & Sun, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-64226-7 · Cited by 76 · see citing works
Peripheral Administration of Fetuin-A Attenuates Early Cerebral Ischemic Injury in Rats
Wang, H., Li, W., Zhu, S., Li, J., D’Amore, J., Ward, M. F., Yang, H., Wu, R., Jahnen‐Dechent, W., Tracey, K. J., et al. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.247 · Cited by 75 · see citing works
Self-citationFetuin protects the fetus from TNF
Wang, H., Zhang, M., Soda, K., Sama, A., & Tracey, K. J. (1997) · The Lancet · doi:10.1016/s0140-6736(05)62030-2 · Cited by 74 · see citing works
Self-citationPolyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity
Chia, T.-Y., Zolp, A. J., & Miska, J. M. (2022) · Cells · doi:10.3390/cells11050896 · Cited by 75 · see citing works
Molecular interactions between the intestinal microbiota and the host
Hertli, S., & Zimmermann, P. (2022) · Molecular Microbiology · doi:10.1111/mmi.14905 · Cited by 76 · see citing works
Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity
Xu, H., Zhang, X., Wang, X., Li, B., Yu, H., Quan, Y., Jiang, Y., You, Y., Wang, Y., Wen, M., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.05.025 · Cited by 73 · see citing works
Lee, Y., Han, O. K., Park, C. W., Suh, S. I., Shin, S. W., Yang, C. H., Jeon, T. W., Lee, E. S., Kim, K. J., Kim, S. H., et al. (2003) · Journal of Ethnopharmacology · doi:10.1016/s0378-8741(02)00298-2 · Cited by 70 · see citing works
Antioxidant capacity of soymilk yogurt and exopolysaccharides produced by lactic acid bacteria
YAMAMOTO, N., SHOJI, M., HOSHIGAMI, H., Watanabe, K., Watanabe, K., TAKATSUZU, T., Yasuda, S., Igoshi, K., & KINOSHITA, H. (2019) · Bioscience of Microbiota Food and Health · doi:10.12938/bmfh.18-017 · Cited by 68 · see citing works
Arginase Activity Mediates Retinal Inflammation in Endotoxin-Induced Uveitis
Zhang, W., Baban, B., Rojas, M., Tofigh, S., Virmani, S. K., Patel, C., Behzadian, M. A., Romero, M. J., Caldwell, R. W., & Caldwell, R. B. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081115 · Cited by 67 · see citing works
Alexander, E. T., Mariner, K., Donnelly, J., Phanstiel, O., & Gilmour, S. K. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-1116 · Cited by 66 · see citing works
Impact of LKM512 yogurt on improvement of intestinal environment of the elderly
Matsumoto, M., Ohishi, H., & Benno, Y. (2001) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2001.tb00518.x · Cited by 66 · see citing works
Intracellular Polyamine Levels of Intestinal Epithelial Cells in Inflammatory Bowel Disease
Weiß, T. S., Herfarth, H. H., Obermeier, F., Ouart, J., Vogl, D., Schölmerich, J., Jauch, K. ‐., & Rogler, G. (2004) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200409000-00006 · Cited by 66 · see citing works
Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats
Motawi, T. K., Abdelgawad, H. M., & Shahin, N. N. (2007) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20194 · Cited by 65 · see citing works
Matsumoto, M., Kitada, Y., & Naito, Y. (2019) · Nutrients · doi:10.3390/nu11051188 · Cited by 65 · see citing works
Estrada, J. A., & Contreras, I. (2019) · Nutrients · doi:10.3390/nu11051076 · Cited by 65 · see citing works
Integrated analysis of gut microbiome and host immune responses in COVID-19
Xu, X., Zhang, W., Guo, M., Xiao, C., Fu, Z., Yu, S., Jiang, L., Wang, S., Ling, Y., Liu, F., et al. (2022) · Frontiers of Medicine · doi:10.1007/s11684-022-0921-6 · Cited by 65 · see citing works
Chaturvedi, R., de Sablet, T., Coburn, L. A., Gobert, A. P., & Wilson, K. T. (2011) · Amino Acids · doi:10.1007/s00726-011-1038-4 · Cited by 62 · see citing works
Identification of Macrophage Arginase I as a New Candidate Gene of Atherosclerosis Resistance
Teupser, D., Burkhardt, R., Wilfert, W., Haffner, I., Nebendahl, K., & Thiery, J. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000195791.83380.4c · Cited by 61 · see citing works
Microbial Metabolite Regulation of Epithelial Cell-Cell Interactions and Barrier Function
Ornelas, A., Dowdell, A. S., Lee, J. S., & Colgan, S. P. (2022) · Cells · doi:10.3390/cells11060944 · Cited by 64 · see citing works
Food Polyamine and Cardiovascular Disease -An Epidemiological Study-
Soda, K., Kano, Y., & Chiba, F. (2012) · Global Journal of Health Science · doi:10.5539/gjhs.v4n6p170 · Cited by 60 · see citing works
Self-citation
- Authors
- Zhang, M., Caragine, T., Wang, H., Cohen, P. S., Botchkina, G., Soda, K., Bianchi, M., Ulrich, P., Cerami, A., Sherry, B., & Tracey, K. J.
- Affiliations
- North Shore University Hospital (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1997-05-19
- Volume
- 185
- Issue
- 10
- Pages
- 1759-1768
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2196317
- OpenAlex
- W2147886921
- Cited by
- 317
- References
- 65
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 11 · 2023: 16 · 2022: 24 · 2021: 18 · 2020: 18 · 2019: 15 · 2018: 11 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 12 · 2013: 9 · 2012: 11
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- spermine, inflammatory cytokines, cytokine synthesis inhibition, monocytes, macrophages, lipopolysaccharide stimulation, TNF-α, interleukin-1, interleukin-6, MIP-1α, MIP-1β, innate immune response, counterregulation, carrageenan-induced inflammation, polyamines, post-transcriptional regulation
- MeSH terms
- Animals, Carrageenan, Cell Line, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Homeostasis, Humans, Inflammation, Interleukin-1, Kinetics, Lipopolysaccharides, Macrophages, Mice, Inbred C3H, Monocytes, Spermine, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Macrophage Inflammatory Proteins, Mice, Chemokine CCL3, Chemokine CCL4
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