Rheumatoid arthritis is a chronic systemic autoimmune disease. The inflammatory response caused by the abnormal activation of the immune system will lead to the formation of pannus in the synovium of the joints, and the gradual destruction of bone and cartilage. The clinical manifestations are pain and swelling of multiple joints, or even deformity, affect the quality of life of patients, and eventually lead to loss of joint function. The main reason for its onset and recurrence is that the immune system produces immune cells, cytokines and antibodies against self-antigens, among which the NLRP3 inflammasome plays a key role in the inflammatory response. As a binding protein of NLRP3, NEK7 kinase acts downstream of K+ efflux and regulates the oligomerization and activation of NLRP3 inflammasomes. However, there have been no report on the involvement of NEK7 in the inflammatory activities of rheumatoid arthritis through the activation of NLRP3 inflammasomes. This article reviews the research progress of NLRP3 inflammasome activation and NEK7 kinase regulating the process of NLRP3 inflammasome activation, in order to provide new insights for the understanding of NLRP3 inflammasome activation by NEK7 on inflammatory activity in rheumatoid arthritis and future research related to targeted therapy.
[1] Chen Z,Bozec A,Ramming A,et al. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis[J].Nat Rev Rheumatol,2019,15(1): 9-17.
[2] 崔轶霞,赵枫,张娜娜,等. 外周血NLRP3炎症小体表达和Th细胞亚群变化与类风湿关节炎患者的生活质量和关节功能的关联[J].临床和实验医学杂志,2021,20(16):1716-1719.
[3] Wu ZM,Luo J,Shi XD,et al. Icariin alleviates rheumatoid arthritis via regulating miR-223-3p/NLRP3 signalling axis[J].Autoimmunity,2020,53(8): 450-458.
[4] Zhang B,Wang B,Cao SH,et al. Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation[J].Int J Mol Med,2017,39(5): 1111-1118.
[5] Esposito E,Cuzzocrea S. TNF-alpha as a therapeutic target in inflammatory diseases,ischemia-reperfusion injury and trauma[J].Curr Med Chem,2009,16(24): 3152-3167.
[6] 李雪,韦翊,陆红梅,等. NLRP3炎症小体与自身免疫性疾病的相关性研究进展[J].现代生物医学进展,2017,17(31):6183-6185.
[7] Pope R M,Tschopp J. The role of interleukin-1 and the inflammasome in gout: implications for therapy[J].Arthritis Rheum,2007,56(10): 3183-3188.
[8] Kim SK,Choe JY,LEE GH. Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjögren's syndrome[J].Clin Chim Acta,2017,474: 147-154.
[9] Li Z,Guo JL,Bi LQ. Role of the NLRP3 inflammasome in autoimmune diseases[J].Biomedecine Pharmacother,2020,130: 110542.
[10] Kim JJ,Jo EK. NLRP3 inflammasome and host protection against bacterial infection[J].J Korean Med Sci,2013,28(10): 1415-1423.
[11] Liu YX,Wei W,Wang Y,et al. TNF-α/calreticulin dual signaling induced NLRP3 inflammasome activation associated with HuR nucleocytoplasmic shuttling in rheumatoid arthritis[J].Inflamm Res,2019,68(7): 597-611.
[12] Guo HT,Callaway JB,Ting JPY. Inflammasomes: mechanism of action,role in disease,and therapeutics[J].Nat Med,2015,21(7): 677-687.
[13] 佟颖,孙乐,刁志惠,等. Nek7与NLRP3炎性小体激活机制的研究进展[J].生命的化学,2018,38(3):367-372.
[14] Lu A,Magupalli VG,Ruan JB,et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes[J].Cell,2014,156(6): 1193-1206.
[15] Cai X,Chen JQ,Xu H,et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation[J].Cell,2014,156(6): 1207-1222.
[16] Guo C,Fu R,Wang S,et al. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis[J].Clin Exp Immunol,2018,194(2): 231-243.
[17] Siebert S,Tsoukas A,Robertson J,et al. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases[J].Pharmacol Rev,2015,67(2): 280-309.
[18] Franchi L,Eigenbrod T,Muoz-Planillo R,et al. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis[J].Nat Immunol,2009,10(3): 241-247.
[19] Liu GL,Chen XL,Wang QQ,et al. NEK7: a potential therapy target for NLRP3-related diseases[J].Biosci Trends,2020,14(2): 74-82.
[20] Kolly L,Busso N,Palmer G,et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium[J].Immunology,2010,129(2): 178-185.
[21] 赵紫琴,徐瑾,王瑞琳,等. 类风湿性关节炎滑膜组织中NLRP3炎性小体及下游因子IL-1β/IL-18的表达及意义[J].临床与实验病理学杂志,2019,35(5):534-538.
[22] Thwaites RS,Unterberger S,Chamberlain G,et al. Expression of sterile-α and armadillo motif containing protein (SARM) in rheumatoid arthritis monocytes correlates with TLR2-induced IL-1β and disease activity[J].Rheumatology (Oxford),2021,60(12): 5843-5853.
[23] Guo WJ,Liu W,Jin B,et al. Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation[J].Int Immunopharmacol,2015,24(2): 232-238.
[24] 廖松林. 现代诊断病理学手册[M].2版.北京:北京大学医学出版社,2015.
[25] He Y,Zeng MY,Yang DH,et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux[J].Nature,2016,530(7590): 354-357.
[26] Xu J,Lu LQ,Li LF. NEK7: a novel promising therapy target for NLRP3-related inflammatory diseases[J].Acta Biochim Biophys Sin (Shanghai),2016,48(10): 966-968.
[27] Zhang YF,Zheng Y,Li HB. NLRP3 inflammasome plays an important role in the pathogenesis of collagen-induced arthritis[J].Mediators Inflamm,2016,2016: 9656270.
[28] Li XF,Shen WW,Sun YY,et al. MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes[J].Joint Bone Spine,2016,83(6): 695-700.
[29] Ruscitti P,Cipriani P,Di Benedetto P,et al. Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients[J].Clin Exp Immunol,2015,182(1): 35-44.
[30] Lasithiotaki I,Giannarakis I,Tsitoura E,et al. NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung[J].Eur Respir J,2016,47(3): 910-918.
