NLRP1 and NLRP3 inflammasomes mediate LPS/ATP-induced pyroptosis in knee osteoarthritis
NLRP1 and NLRP3 inflammasomes mediate LPS/ATP-induced pyroptosis in knee osteoarthritis
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DOI：
10.3892/mmr.2018.8520
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Zhao, Ling-Rui;Xing, Run-Lin;Zhang, Li
炎性细胞凋亡是由炎性小体在各种炎症刺激（包括脂多糖（LPS）和不适当的pH）激活后触发的。这可能导致受影响细胞的程序性死亡。众所周知，NLRP 1和NLRP 3炎性小体介导炎症性疾病中多种细胞因子的产生;然而，NLRP 1和NLRP 3炎性小体是否能够影响膝骨关节炎（KOA）进展中LPS诱导的细胞凋亡仍是未知的。在本研究中，NLRP炎性小体和成纤维细胞样滑膜细胞（FLS）之间的相关性进行了研究，在体内和体外。从KOA患者收集人滑膜样品，并分析NLRP 1和NLRP 3炎性体的表达。在体外分离人FLS并用LPS刺激。为了确定NLRP 1和NLRP 3炎性小体是否参与FLS焦亡，使用NLRP 1和NLRP 3小干扰RNA（siRNA）。结果表明，LPS+ATP刺激FLS后，NLRPs和炎性小体相关蛋白表达上调，FLS细胞发生焦亡。然而，LPS+ ATP诱导的焦亡被NLRP 1和NLRP 3 siRNA减弱。本研究的结果表明，LPS诱导的FLS焦亡可能是由NLRP 1或NLRP 3炎性小体介导的。总之，基于从患者和体外细胞获得的数据，本研究结果表明NLRP 1和NLRP 3炎性小体高度参与FLS炎症和焦亡。此外，NLRP 1和NLRP 3的抑制导致了与脓毒症相关的细胞因子的显著减少。因此，NLRP 1和NLRP 3炎性体可能在OA的发病机制中很重要，并且可能代表一种新的治疗靶点。
Pyroptosis is triggered by inflammasomes after its activation by various inflammatory stimulations, including lipopolysaccharide (LPS) and improper pH. This may result in programmed death of the affected cell. It is well known that NLRP1 and NLRP3 inflammasomes mediate the production of various cytokines in inflammatory disorders; however, it is still unknown whether NLRP1 and NLRP3 inflammasomes can influence the LPS-induced pyroptosis in the progression of knee osteoarthritis (KOA). In the present study, the correlation between the NLRP inflammasomes and fibroblast-like synoviocytes (FLSs) pyroptosis was investigated in vivo and in vitro. Human synovial samples were collected from KOA patients and the expression of NLRP1 and NLRP3 inflammasomes was analyzed. Human FLS were isolated in vitro and stimulated with LPS. To determine whether NLRP1 and NLRP3 inflammasomes are involved in FLS pyroptosis, NLRP1 and NLRP3 small interfering RNAs (siRNAs) were used. The results showed that the expression of NLRPs and inflammasome-related proteins were upregulated and FLS stimulated with LPS+ATP resulted in cell pyroptosis. However, LPS+ATP-induced pyroptosis was attenuated by NLRP1 and NLRP3 siRNAs. The results of the present study indicate that LPS-induced FLS pyroptosis may be mediated by either NLRP1 or NLRP3 inflammsomes. Overall, based on the data obtained from patients and in vitro cells, the present finsings showed that NLRP1 and NLRP3 inflammasomes are highly involved in the FLS inflammation and pyroptosis. Furthermore, inhibition of NLRP1 and NLRP3 led to a remarkable reduction of pyroptosis-related cytokines. Thus, NLRP1 and NLRP3 inflammasomes may be important in the pathogenesis of OA and may represent a novel therapeutic target.