国际口腔医学杂志 ›› 2022, Vol. 49 ›› Issue (1): 85-93.doi: 10.7518/gjkq.2022022

• 综述 • 上一篇    下一篇

特异性促炎症消退介质在牙周炎中作用的研究进展

白慧敏(),张雨薇,孟姝,刘程程()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院牙周病科 成都 610041
  • 收稿日期:2021-03-22 修回日期:2021-09-11 出版日期:2022-01-01 发布日期:2022-01-07
  • 通讯作者: 刘程程
  • 作者简介:白慧敏,硕士,Email: bhmkq123@163.com
  • 基金资助:
    国家自然科学基金(81600871)

Research progress on the role of specialized pro-resolving mediators in periodontitis

Bai Huimin(),Zhang Yuwei,Meng Shu,Liu Chengcheng()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Di-seases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2021-03-22 Revised:2021-09-11 Online:2022-01-01 Published:2022-01-07
  • Contact: Chengcheng Liu
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81600871)

摘要:

牙周炎是由牙菌斑生物膜引起的牙周支持组织的慢性炎症性疾病。特异性促炎症消退介质(SPM)是由多不饱和脂肪酸经酶促反应衍生而来的脂质介质,可积极调控炎症的消退,改变微生物组成,缓解疼痛并促进组织再生,有望在牙周炎防治中发挥辅助作用。本文就SPM的分类及作用机制进行综述,并总结了其在牙周组织炎症过程中作用的最新研究进展,以期为牙周炎发生发展机制的研究提供参考,为牙周炎的防治提供新的思路。

关键词: 牙周炎, 特异性促炎症消退介质, 消退素, 脂氧素, 保护素

Abstract:

Periodontitis is a chronic inflammatory disease of periodontal supporting tissues initiated by oral biofilm. Specialised pro-resolving mediators (SPMs) are mediators derived from polyunsaturated fatty acids, and they can actively regulate the resolution of inflammation, change microbial composition, reduce pain and promote tissue regeneration. SPMs may serve as auxiliary means for the prevention and treatment of periodontal diseases. This paper summarised the classification and mechanism of SPMs and reviewed the latest research progress on its role in periodontal tissue inflammation and repair. This study aims to provide ideas and reference for further study on the mechanisms of the development of periodontitis and enhance the prevention and treatment of periodontitis.

Key words: periodontitis, specialized pro-resolving mediators, resolvin, lipoxin, protectin

表 1

消退素及相应受体"

消退素 消退素受体基因 参考文献
RvD2 GPR18 [13]
RvD1、RvD3和RvD5 GPR32 [14-16]
RvD1、RvD3 FPR2/ALXR [14,17]
RvE1、RvE2 ChemR23 [18-19]
RvE1和RvE2 BLT1 [18-19]
[1] van Dyke TE, Sima C. Understanding resolution of inflammation in periodontal diseases: is chronic inflammatory periodontitis a failure to resolve[J]. Periodontol 2000, 2020,82(1):205-213.
[2] Buckley CD, Gilroy DW, Serhan CN, et al. The re-solution of inflammation[J]. Nat Rev Immunol, 2013,13(1):59-66.
[3] Serhan CN, Gupta SK, Perretti M, et al. The atlas of inflammation resolution (AIR)[J]. Mol Aspects Med, 2020,74:100894.
[4] Decker C, Sadhu S, Fredman G. Pro-resolving ligands orchestrate phagocytosis[J]. Front Immunol, 2021,12:660865.
[5] 孟焕新, 张立. 牙周临床治疗Ⅰ.侵袭性牙周炎的诊断及治疗[J]. 中华口腔医学杂志, 2005,40(1):81-84.
Meng HX, Zhang L. Treatment of periodontol disease:part I.Diagnosis and treatment of aggressive periodontitis[J]. Chin J Stomatol, 2005,40(1):81-84.
[6] Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions[J]. Nat Rev Microbiol, 2018,16(12):745-759.
[7] Ali M, Yang F, Jansen JA, et al. Lipoxin suppresses inflammation via the TLR4/MyD88/NF-κB pathway in periodontal ligament cells[J]. Oral Dis, 2020,26(2):429-438.
[8] Ye Y, Zhang HW, Mei HX, et al. PDX regulates inflammatory cell infiltration via resident macrophage in LPS-induced lung injury[J]. J Cell Mol Med, 2020,24(18):10604-10614.
[9] Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators[J]. J Clin Invest, 2018,128(7):2657-2669.
[10] Reinertsen AF, Primdahl KG, Shay AE, et al. Stereoselective synjournal and structural confirmation of the specialized pro-resolving mediator resolvin E4[J]. J Org Chem, 2021,86(4):3535-3545.
[11] Dalli J, Chiag N, Serhan CN. Elucidation of novel 13-series resolvins that increase with atorvastatin and c-lear infections[J]. Nat Med, 2015,21(9):1071-1075.
[12] Chiang N, Serhan CN. Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors[J]. Mol Aspects Med, 2017,58:114-129.
[13] Chiang N, Dalli J, Colas RA, et al. Identification of resolvin D2 receptor mediating resolution of infections and organ protection[J]. J Exp Med, 2015,212(8):1203-1217.
[14] Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs[J]. Am J Pathol, 2012,180(5):2018-2027.
[15] Dalli J, Winkler JW, Colas RA, et al. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents[J]. Chem Biol, 2013,20(2):188-201.
[16] Chiang N, Fredman G, Bäckhed F, et al. Infection regulates pro-resolving mediators that lower antibiotic requirements[J]. Nature, 2012,484(7395):524-528.
[17] Arnardottir HH, Dalli J, Norling LV, et al. Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation[J]. J Immunol, 2016,197(6):2362-2368.
[18] Arita M, Ohira T, Sun YP, et al. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation[J]. J Immunol, 2007,178(6):3912-3917.
[19] Oh SF, Dona M, Fredman G, et al. Resolvin E2 formation and impact in inflammation resolution[J]. J Immunol, 2012,188(9):4527-4534.
[20] Mizraji G, Heyman O, van Dyke TE, et al. Resolvin D2 restrains Th1 immunity and prevents alveolar bone loss in murine periodontitis[J]. Front Immunol, 2018,9:785.
[21] Mustafa M, Zarrough A, Bolstad AI, et al. Resolvin D1 protects periodontal ligament[J]. Am J Physiol Cell Physiol, 2013,305(6):C673-C679.
[22] Chiang N, de la Rosa X, Libreros S, et al. Novel resolvin D2 receptor axis in infectious inflammation[J]. J Immunol, 2017,198(2):842-851.
[23] Chiurchiù V, Leuti A, Dalli J, et al. Proresolving lipid mediators resolvin D1, resolvin D2, maresin 1 are critical in modulating T cell responses[J]. Sci Transl Med, 2016, 8(353): 353ra111.
[24] Cheng T, Ding S, Liu SS, et al. Resolvin D1 improves the treg/Th17 imbalance in systemic lupus erythematosus through miR-30e-5p[J]. Front Immunol, 2021,12:668760.
[25] Ramon S, Gao F, Serhan CN, et al. Specialized proresolving mediators enhance human B cell differentiation to antibody-secreting cells[J]. J Immunol, 2012,189(2):1036-1042.
[26] Maekawa T, Hosur K, Abe T, et al. Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway[J]. Nat Commun, 2015,6:8272.
[27] 程抒华, 徐华兴, 陈杰, 等. 消退素E1调控牙周膜成纤维细胞改善牙周组织炎症的研究[J]. 口腔生物医学, 2019,10(2):68-72.
Cheng SH, Xu XH, Chen J, et al. Effects of resolvin E1 on periodontal ligament cells in experimental periodontitis[J]. Oral Biomed, 2019,10(02):68-72.
[28] Serhan CN, Chiang N, Dalli J. The resolution code of a-cute inflammation: novel pro-resolving lipid mediators in resolution[J]. Semin Immunol, 2015,27(3):200-215.
[29] Fredman G, Oh SF, Ayilavarapu S, et al. Impaired phagocytosis in localized aggressive periodontitis: rescue by resolvin E1[J]. PLoS One, 2011,6(9):e24422.
[30] Hasturk H, Kantarci A, Ohira T, et al. RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis[J]. FASEB J, 2006,20(2):401-403.
[31] Lee CT, Teles R, Kantarci A, et al. Resolvin E1 reverses experimental periodontitis and dysbiosis[J]. J Immunol, 2016,197(7):2796-2806.
[32] Hasturk H, Kantarci A, Goguet-Surmenian E, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo[J]. J Immunol, 2007,179(10):7021-7029.
[33] Alvarez C, Abdalla H, Sulliman S, et al. RvE1 impacts the gingival inflammatory infiltrate by inhibiting the T cell response in experimental periodontitis[J]. Front Immunol, 2021,12:664756.
[34] Dalli J, Zhu M, Vlasenko NA, et al. The novel 13S, 14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype[J]. FASEB J, 2013,27(7):2573-2583.
[35] Freire MO, van Dyke TE. Natural resolution of inflammation[J]. Periodontol 2000, 2013,63(1):149-164.
[36] van Dyke TE. The management of inflammation in periodontal disease[J]. J Periodontol, 2008,79(8 Suppl):1601-1608.
[37] Cianci E, Recchiuti A, Trubiani O, et al. Human periodontal stem cells release specialized proresol-ving mediators and carry immunomodulatory and prohealing properties regulated by lipoxins[J]. Stem Cells Transl Med, 2016,5(1):20-32.
[38] Pouliot M, Clish CB, Petasis NA, et al. Lipoxin A4 analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease[J]. Biochemistry, 2000,39(16):4761-4768.
[39] Serhan CN, Jain A, Marleau S, et al. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators[J]. J Immunol, 2003,171(12):6856-6865.
[40] Lawrence T, Gilroy DW. Chronic inflammation: a failure of resolution[J]. Int J Exp Pathol, 2007,88(2):85-94.
[41] Ali M, Kucko N, Jansen JA, et al. The effect of lipoxin A4 on E. coli LPS-induced osteoclastogenesis[J]. Clin Oral Investig, 2021,25(3):957-969.
[42] Mitchell S, Thomas G, Harvey K, et al. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo[J]. J Am Soc Nephrol, 2002,13(10):2497-2507.
[43] Zhao J, Geng WJ, Wan KF, et al. Lipoxin A4 promotes autophagy and inhibits overactivation of macrophage inflammasome activity induced by Pg LPS[J]. J Int Med Res, 2021,49(2):300060520981259.
[44] Chen P, Fenet B, Michaud S, et al. Full characterization of PDX, a neuroprotectin/protectin D1 isomer, which inhibits blood platelet aggregation[J]. FEBS Lett, 2009,583(21):3478-3484.
[45] Serhan CN, Fredman G, Yang R, et al. Novel proresolving aspirin-triggered DHA pathway[J]. Chem Biol, 2011,18(8):976-987.
[46] Serhan CN, Gotlinger K, Hong S, et al. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes[J]. J Immunol, 2006,176(3):1848-1859.
[47] Bang SS, Xie YK, Zhang ZJ, et al. GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain[J]. J Clin Invest, 2018,128(8):3568-3582.
[48] Bosviel R, Joumard-Cubizolles L, Chinetti-Gbaguidi G, et al. DHA-derived oxylipins, neuroprostanes and protectins, differentially and dose-dependently modulate the inflammatory response in human macrophages: putative mechanisms through PPAR activation[J]. Free Radic Biol Med, 2017,103:146-154.
[49] Tang S, Wan M, Huang W, et al. Maresins: specialized proresolving lipid mediators and their potential role in inflammatory-related diseases[J]. Mediators Inflamm, 2018,2018:2380319.
[50] Chiang N, Libreros S, Norris PC, et al. Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions[J]. J Clin Invest, 2019,129(12):5294-5311.
[51] Marcon R, Bento AF, Dutra RC, et al. Maresin 1, a proresolving lipid mediator derived from Omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis[J]. J Immunol, 2013,191(8):4288-4298.
[52] Deng B, Wang CW, Arnardottir HH, et al. Maresin biosynjournal and identification of maresin 2, a new anti-inflammatory and pro-resolving mediator from human macrophages[J]. PLoS One, 2014,9(7):e10-2362.
[53] Wang CW, Yu SH, Fretwurst T, et al. Maresin 1 promotes wound healing and socket bone regeneration for alveolar ridge preservation[J]. J Dent Res, 2020,99(8):930-937.
[54] Albuquerque-Souza E, Schulte F, Chen T, et al. Maresin-1 and resolvin E1 promote regenerative properties of periodontal ligament stem cells under inflammatory conditions[J]. Front Immunol, 2020,11:585530.
[55] Qiu Y, Wu YC, Zhao HM, et al. Maresin 1 mitigates renal ischemia/reperfusion injury in mice via inhibition of the TLR4/MAPK/NF-κB pathways and activation of the Nrf2 pathway[J]. Drug Des Devel Ther, 2019,13:739-745.
[56] Dalli J, Ramon S, Norris PC, et al. Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathways[J]. FASEB J, 2015,29(5):2120-2136.
[57] Dalli J, Vlasakov I, Riley IR, et al. Maresin conjugates in tissue regeneration biosynjournal enzymes in human macrophages[J]. Proc Natl Acad Sci U S A, 2016,113(43):12232-12237.
[58] Dalli J, Colas RA, Arnardottir H, et al. Vagal regulation of group 3 innate lymphoid cells and the immunoresolvent PCTR1 controls infection resolution[J]. Immunity, 2017,46(1):92-105.
[59] Rosenstein ED, Kushner LJ, Kramer N, et al. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis[J]. Prostaglandins Leukot Essent Fatty Acids, 2003,68(3):213-218.
[60] Kesavalu L, Vasudevan B, Raghu B, et al. Omega-3 fatty acid effect on alveolar bone loss in rats[J]. J Dent Res, 2006,85(7):648-652.
[61] El-Sharkawy H, Aboelsaad N, Eliwa M, et al. Adjunctive treatment of chronic periodontitis with daily dietary supplementation with Omega-3 Fatty acids and low-dose aspirin[J]. J Periodontol, 2010,81(11):1635-1643.
[62] Castro Dos Santos NC, Andere NMRB, Araujo CF, et al. Omega-3 PUFA and aspirin as adjuncts to periodontal debridement in patients with periodontitis and type 2 diabetes mellitus: randomized clinical trial[J]. J Periodontol, 2020,91(10):1318-1327.
[63] Clish CB, O’Brien JA, Gronert K, et al. Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo[J]. Proc Natl Acad Sci U S A, 1999,96(14):8247-8252.
[64] van Dyke TE, Hasturk H, Kantarci A, et al. Proresolving nanomedicines activate bone regeneration in periodontitis[J]. J Dent Res, 2015,94(1):148-156.
[65] Wang B, Booij-Vrieling HE, Bronkhorst EM, et al. Antimicrobial and anti-inflammatory thermo-rever-sible hydrogel for periodontal delivery[J]. Acta Biomater, 2020,116:259-267.
[66] Ali M, Yang F, Plachokova AS, et al. Application of specialized pro-resolving mediators in periodontitis and peri-implantitis: a review[J]. Eur J Oral Sci, 2021,129(1):e12759.
[67] Osorio Parra MM, Elangovan S, Lee CT. Specia-lized pro-resolving lipid mediators in experimental periodontitis: a systematic review[J]. Oral Dis, 2019,25(5):1265-1276.
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