特异性促炎症消退介质干预溃疡性结肠炎的研究进展
Specialized Pro-Resolving Mediators: Unveiling Their Role in Ulcerative Colitis
DOI: 10.12677/pi.2024.134047, PDF,   
作者: 郭鹏翔, 戴 岳*：中国药科大学中药学院中药药理与中医药学系，江苏 南京
关键词: 特异性促炎症消退介质；溃疡性结肠炎；消退素；脂氧素；保护素；Specialized Pro-Resolving Mediators； Ulcerative Colitis； Resolvins； Lipoxins； Protectins
摘要: 近年来，特异性促炎症消退介质(SPMs)对溃疡性结肠炎(UC)的影响日益受到关注。SPMs通过加速中性粒细胞清除、促进胞葬和修复上皮缺损等途径，促进结肠炎症的消退。本文就SPMs的分类及作用进行综述，关注其在UC中的最新研究进展，旨在为揭示UC的发病机制和构建靶向治疗策略提供参考。
Abstract: Recently, there has been a growing focus on the role of specialized pro-resolving mediators (SPMs) in ulcerative colitis (UC). SPMs facilitate the resolution of colonic inflammation by accelerating neutrophil clearance, promoting efferocytosis, and facilitating epithelial repair. These functions offer novel insights into the treatment of UC. This article provides a comprehensive review of the classification and mechanisms of action of SPMs. It also summarizes the latest research advances in their role in UC. The aim is to establish a theoretical basis and suggest new research directions for future therapeutic strategies.
文章引用：郭鹏翔, 戴岳. 特异性促炎症消退介质干预溃疡性结肠炎的研究进展[J]. 药物资讯, 2024, 13(4): 398-404. https://doi.org/10.12677/pi.2024.134047

参考文献

[1] Sugimoto, M.A., Vago, J.P., Perretti, M. and Teixeira, M.M. (2019) Mediators of the Resolution of the Inflammatory Response. Trends in Immunology, 40, 212-227. [Google Scholar] [CrossRef] [PubMed]
[2] Perretti, M., Leroy, X., Bland, E.J. and Montero-Melendez, T. (2015) Resolution Pharmacology: Opportunities for Therapeutic Innovation in Inflammation. Trends in Pharmacological Sciences, 36, 737-755. [Google Scholar] [CrossRef] [PubMed]
[3] Chiang, N., Fredman, G., Bäckhed, F., Oh, S.F., Vickery, T., Schmidt, B.A., et al. (2012) Infection Regulates Pro-Resolving Mediators that Lower Antibiotic Requirements. Nature, 484, 524-528. [Google Scholar] [CrossRef] [PubMed]
[4] Fullerton, J.N. and Gilroy, D.W. (2016) Resolution of Inflammation: A New Therapeutic Frontier. Nature Reviews Drug Discovery, 15, 551-567. [Google Scholar] [CrossRef] [PubMed]
[5] Quiros, M. and Nusrat, A. (2019) Saving Problematic Mucosae: SPMs in Intestinal Mucosal Inflammation and Repair. Trends in Molecular Medicine, 25, 124-135. [Google Scholar] [CrossRef] [PubMed]
[6] Radbakhsh, S., Katsiki, N., Santos, R.D., Mikhailidis, D.P., Mantzoros, C.S. and Sahebkar, A. (2022) Effects of Statins on Specialized Pro-Resolving Mediators: An Additional Pathway Leading to Resolution of Inflammation. Metabolism, 132, Article 155211. [Google Scholar] [CrossRef] [PubMed]
[7] Le Berre, C., Honap, S. and Peyrin-Biroulet, L. (2023) Ulcerative Colitis. The Lancet, 402, 571-584. [Google Scholar] [CrossRef] [PubMed]
[8] Jairath, V. and Feagan, B.G. (2020) Global Burden of Inflammatory Bowel Disease. The Lancet Gastroenterology & Hepatology, 5, 2-3. [Google Scholar] [CrossRef] [PubMed]
[9] Al-Horani, R., Spanudakis, E. and Hamad, B. (2021) The Market for Ulcerative Colitis. Nature Reviews Drug Discovery, 21, 15-16. [Google Scholar] [CrossRef] [PubMed]
[10] Serhan, C.N. and Levy, B.D. (2018) Resolvins in Inflammation: Emergence of the Pro-Resolving Superfamily of Mediators. Journal of Clinical Investigation, 128, 2657-2669. [Google Scholar] [CrossRef] [PubMed]
[11] Serhan, C.N., Chiang, N., Dalli, J. and Levy, B.D. (2014) Lipid Mediators in the Resolution of Inflammation. Cold Spring Harbor Perspectives in Biology, 7, a016311. [Google Scholar] [CrossRef] [PubMed]
[12] Pistorius, K., Souza, P.R., De Matteis, R., Austin-Williams, S., Primdahl, K.G., Vik, A., et al. (2018) PDn-3 DPA Pathway Regulates Human Monocyte Differentiation and Macrophage Function. Cell Chemical Biology, 25, 749-760. [Google Scholar] [CrossRef] [PubMed]
[13] Gobbetti, T., Dalli, J., Colas, R.A., Federici Canova, D., Aursnes, M., Bonnet, D., et al. (2017) Protectin D1n-3 DPA and Resolvin D5n-3 DPA Are Effectors of Intestinal Protection. Proceedings of the National Academy of Sciences of the United States of America, 114, 3963-3968. [Google Scholar] [CrossRef] [PubMed]
[14] Campbell, E.L., MacManus, C.F., Kominsky, D.J., Keely, S., Glover, L.E., Bowers, B.E., et al. (2010) Resolvin E1-Induced Intestinal Alkaline Phosphatase Promotes Resolution of Inflammation through LPS Detoxification. Proceedings of the National Academy of Sciences of the United States of America, 107, 14298-14303. [Google Scholar] [CrossRef] [PubMed]
[15] Panigrahy, D., Gilligan, M.M., Serhan, C.N. and Kashfi, K. (2021) Resolution of Inflammation: An Organizing Principle in Biology and Medicine. Pharmacology & Therapeutics, 227, Article 107879. [Google Scholar] [CrossRef] [PubMed]
[16] Wan, M., Godson, C., Guiry, P.J., Agerberth, B. and Haeggström, J.Z. (2011) Leukotriene B4/Antimicrobial Peptide LL-37 Proinflammatory Circuits Are Mediated by BLT1 and FPR2/ALX and Are Counterregulated by Lipoxin A4 and Resolvin E1. The FASEB Journal, 25, 1697-1705. [Google Scholar] [CrossRef] [PubMed]
[17] Arita, M., Yoshida, M., Hong, S., Tjonahen, E., Glickman, J.N., Petasis, N.A., et al. (2005) Resolvin E1, an Endogenous Lipid Mediator Derived from Omega-3 Eicosapentaenoic Acid, Protects against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis. Proceedings of the National Academy of Sciences of the United States of America, 102, 7671-7676. [Google Scholar] [CrossRef] [PubMed]
[18] Krishnamoorthy, S., Recchiuti, A., Chiang, N., Yacoubian, S., Lee, C., Yang, R., et al. (2010) Resolvin D1 Binds Human Phagocytes with Evidence for Proresolving Receptors. Proceedings of the National Academy of Sciences of the United States of America, 107, 1660-1665. [Google Scholar] [CrossRef] [PubMed]
[19] Chiang, N., Dalli, J., Colas, R.A. and Serhan, C.N. (2015) Identification of Resolvin D2 Receptor Mediating Resolution of Infections and Organ Protection. Journal of Experimental Medicine, 212, 1203-1217. [Google Scholar] [CrossRef] [PubMed]
[20] Sun, Y., Oh, S.F., Uddin, J., Yang, R., Gotlinger, K., Campbell, E., et al. (2007) Resolvin D1 and Its Aspirin-Triggered 17R Epimer: Stereochemical Assignments, Anti-Inflammatory Properties, and Enzymatic Inactivation. Journal of Biological Chemistry, 282, 9323-9334. [Google Scholar] [CrossRef] [PubMed]
[21] Schmid, M., Gemperle, C., Rimann, N. and Hersberger, M. (2016) Resolvin D1 Polarizes Primary Human Macrophages toward a Proresolution Phenotype through GPR32. The Journal of Immunology, 196, 3429-3437. [Google Scholar] [CrossRef] [PubMed]
[22] Lee, H.-N., Choi, Y.-S., Kim, S.H., Zhong, X., Kim, W., Park, J.S., et al. (2021) Resolvin D1 Suppresses Inflammation-Associated Tumorigenesis in the Colon by Inhibiting IL-6-Induced Mitotic Spindle Abnormality. The FASEB Journal, 35, e21432. [Google Scholar] [CrossRef] [PubMed]
[23] Zeng, C., Liu, X., Zhu, S., Xiong, D., Zhu, L., Hou, X., et al. (2022) Resolvin D1 Ameliorates Hepatic Steatosis by Remodeling the Gut Microbiota and Restoring the Intestinal Barrier Integrity in DSS-Induced Chronic Colitis. International Immunopharmacology, 103, Article 108500. [Google Scholar] [CrossRef] [PubMed]
[24] Campbell, E.L., Louis, N.A., Tomassetti, S.E., Canny, G.O., Arita, M., Serhan, C.N., et al. (2007) Resolvin E1 Promotes Mucosal Surface Clearance of Neutrophils: A New Paradigm for Inflammatory Resolution. The FASEB Journal, 21, 3162-3170. [Google Scholar] [CrossRef] [PubMed]
[25] Ishida, T., Yoshida, M., Arita, M., Nishitani, Y., Nishiumi, S., Masuda, A., et al. (2010) Resolvin E1, an Endogenous Lipid Mediator Derived from Eicosapentaenoic Acid, Prevents Dextran Sulfate Sodium-Induced Colitis. Inflammatory Bowel Diseases, 16, 87-95. [Google Scholar] [CrossRef] [PubMed]
[26] Quiros, M., Feier, D., Birkl, D., Agarwal, R., Zhou, D.W., García, A.J., et al. (2020) Resolvin E1 Is a Pro-Repair Molecule that Promotes Intestinal Epithelial Wound Healing. Proceedings of the National Academy of Sciences of the United States of America, 117, 9477-9482. [Google Scholar] [CrossRef] [PubMed]
[27] Chiang, N., Serhan, C.N., Dahlén, S., Drazen, J.M., Hay, D.W.P., Rovati, G.E., et al. (2006) The Lipoxin Receptor ALX: Potent Ligand-Specific and Stereoselective Actions in vivo. Pharmacological Reviews, 58, 463-487. [Google Scholar] [CrossRef] [PubMed]
[28] Levy, B.D., Clish, C.B., Schmidt, B., Gronert, K. and Serhan, C.N. (2001) Lipid Mediator Class Switching during Acute Inflammation: Signals in Resolution. Nature Immunology, 2, 612-619. [Google Scholar] [CrossRef] [PubMed]
[29] Godson, C., Mitchell, S., Harvey, K., Petasis, N.A., Hogg, N. and Brady, H.R. (2000) Cutting Edge: Lipoxins Rapidly Stimulate Nonphlogistic Phagocytosis of Apoptotic Neutrophils by Monocyte-Derived Macrophages. The Journal of Immunology, 164, 1663-1667. [Google Scholar] [CrossRef] [PubMed]
[30] Gewirtz, A.T., Collier-Hyams, L.S., Young, A.N., Kucharzik, T., Guilford, W.J., Parkinson, J.F., et al. (2002) Lipoxin A4 Analogs Attenuate Induction of Intestinal Epithelial Proinflammatory Gene Expression and Reduce the Severity of Dextran Sodium Sulfate-Induced Colitis. The Journal of Immunology, 168, 5260-5267. [Google Scholar] [CrossRef] [PubMed]
[31] Vong, L., Ferraz, J.G.P., Dufton, N., Panaccione, R., Beck, P.L., Sherman, P.M., et al. (2012) Up-Regulation of Annexin-A1 and Lipoxin A4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis. PLOS ONE, 7, e39244. [Google Scholar] [CrossRef] [PubMed]
[32] Ağış, E.R., Savaş, B. and Melli, M. (2015) Impact of Colonic Mucosal Lipoxin A4 Synthesis Capacity on Healing in Rats with Dextran Sodium Sulfate-Induced Colitis. Prostaglandins & Other Lipid Mediators, 121, 63-69. [Google Scholar] [CrossRef] [PubMed]
[33] Serhan, C.N., Gotlinger, K., Hong, S., Lu, Y., Siegelman, J., Baer, T., et al. (2006) Anti-Inflammatory Actions of Neuroprotectin D1/Protectin D1 and Its Natural Stereoisomers: Assignments of Dihydroxy-Containing Docosatrienes. The Journal of Immunology, 176, 1848-1859. [Google Scholar] [CrossRef] [PubMed]
[34] Masterson, J.C., McNamee, E.N., Fillon, S.A., Hosford, L., Harris, R., Fernando, S.D., et al. (2014) Eosinophil-Mediated Signalling Attenuates Inflammatory Responses in Experimental Colitis. Gut, 64, 1236-1247. [Google Scholar] [CrossRef] [PubMed]
[35] Serhan, C.N., Yang, R., Martinod, K., Kasuga, K., Pillai, P.S., Porter, T.F., et al. (2008) Maresins: Novel Macrophage Mediators with Potent Antiinflammatory and Proresolving Actions. Journal of Experimental Medicine, 206, 15-23. [Google Scholar] [CrossRef] [PubMed]
[36] Marcon, R., Bento, A.F., Dutra, R.C., Bicca, M.A., Leite, D.F.P. and Calixto, J.B. (2013) Maresin 1, a Proresolving Lipid Mediator Derived from Omega-3 Polyunsaturated Fatty Acids, Exerts Protective Actions in Murine Models of Colitis. The Journal of Immunology, 191, 4288-4298. [Google Scholar] [CrossRef] [PubMed]
[37] Gu, Z., Lamont, G.J., Lamont, R.J., Uriarte, S.M., Wang, H. and Scott, D.A. (2016) Resolvin D1, Resolvin D2 and Maresin 1 Activate the GSK3β Anti-Inflammatory Axis in TLR4-Engaged Human Monocytes. Innate Immunity, 22, 186-195. [Google Scholar] [CrossRef] [PubMed]
[38] Wang, H., Shi, P., Huang, C., et al. (2016) Maresin 1 Ameliorates Iron-Deficient Anemia in IL-10(-/-) Mice with Spontaneous Colitis by the Inhibition of Hepcidin Expression though the IL-6/STAT3 Pathway. American Journal of Translational Research, 8, 2758-2766.
[39] Miranda, J., Brazil, J.C., Morris, A.H., Parkos, C.A., Quiros, M. and Nusrat, A. (2023) Maresin-2 Promotes Mucosal Repair and Has Therapeutic Potential When Encapsulated in Thermostable Nanoparticles. Proceedings of the National Academy of Sciences of the United States of America, 120, e2218162120. [Google Scholar] [CrossRef] [PubMed]
[40] Chiang, N. and Serhan, C.N. (2020) Specialized Pro-Resolving Mediator Network: An Update on Production and Actions. Essays in Biochemistry, 64, 443-462. [Google Scholar] [CrossRef] [PubMed]
[41] Orr, S.K., Colas, R.A., Dalli, J., Chiang, N. and Serhan, C.N. (2015) Proresolving Actions of a New Resolvin D1 Analog Mimetic Qualifies as an Immunoresolvent. American Journal of Physiology-Lung Cellular and Molecular Physiology, 308, L904-L911. [Google Scholar] [CrossRef] [PubMed]
[42] Torricelli, A.A., Santhanam, A., Agrawal, V., et al. (2014) Resolvin E1 analog RX-10045 0.1% Reduces Corneal Stromal Haze in Rabbits when Applied Topically after PRK. Molecular Vision, 20, 1710-1716.
[43] Fredman, G. and Serhan, C.N. (2011) Specialized Proresolving Mediator Targets for RvE1 and RvD1 in Peripheral Blood and Mechanisms of Resolution. Biochemical Journal, 437, 185-197. [Google Scholar] [CrossRef] [PubMed]
[44] Norling, L.V., Spite, M., Yang, R., Flower, R.J., Perretti, M. and Serhan, C.N. (2011) Cutting Edge: Humanized Nano-Proresolving Medicines Mimic Inflammation-Resolution and Enhance Wound Healing. The Journal of Immunology, 186, 5543-5547. [Google Scholar] [CrossRef] [PubMed]