NOX1/NADPH oxidase is involved in the LPS-induced exacerbation of collagen-induced arthritis
NOX1/NADPH oxidase is involved in the LPS-induced exacerbation of collagen-induced arthritis
复制标题
NOX1/NADPH 氧化酶参与 LPS 诱导的胶原诱导关节炎恶化
DOI：
10.1016/j.jphs.2021.01.009
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Yabe-Nishimura C.
中科院分区：
文献类型：
--
作者：
Matsumoto M;Liu J;Iwata K;Ibi M;Asaoka N;Zhang X;Katsuyama M;Matsuda M;Nabe T;Scroder K;Yabe-Nishimura C.
我们利用NOX1基因敲除小鼠(NOX1-KO)研究了NOX1在免疫反应中的未知作用。NOX1是超氧化物产生NADPH氧化酶的一种非吞噬形式。NOX1的转录产物在淋巴组织中表达，包括脾、胸腺、骨髓和腹股沟淋巴结节。检测卵清蛋白(OVA)免疫后的抗体产生情况，野生型小鼠(WT)和Nox1-KO小鼠的血清抗OVA抗体水平无显著差异。在实验性哮喘中，OVA诱发哮喘后嗜酸性粒细胞的浸润和Th2细胞因子反应在两种基因型之间相似。然而，NOX1-KO组小剂量内毒素(LPS)诱导的实验性胶原诱导性关节炎(CIA)的严重程度和发生率显著低于NOX1-KO组。虽然NOX1缺乏对小鼠血清自身抗体水平和体外细胞因子反应均无影响，但在内毒素攻击后，小鼠脾组织中NOX1mRNA水平显著升高。在脾细胞中，CD11b+单核/巨噬细胞和CD11c+树突状细胞中的NOX1表达均显著上调，提示单核/巨噬细胞/树突状细胞中的NOX1可能参与了实验性CIA的发生发展。因此，NOX1的治疗靶点可以控制因细菌感染而加重的关节炎的发病和/或严重程度。
We investigate as yet an unidentified role of NOX1, a non-phagocytic isoform of the superoxide-generating NADPH oxidase, in immune responses usingNox1-knockout mice (Nox1-KO). The transcripts of NOX1 was expressed in lymphoid tissues, including the spleen, thymus, bone marrow, and inguinal lymphoid nodes. When antibody production after ovalbumin (OVA) immunization was examined, no significant differences were observed in serum anti-OVA IgG levels between wild-type mice (WT) and Nox1-KO. In the experimental asthma, the infiltration of eosinophils and the Th2 cytokine response after the induction of asthma with OVA were similar between the two genotypes. However, the severity and incidence of experimental collagen-induced arthritis (CIA) following the administration of a low dose of endotoxin (LPS) were significantly lower in Nox1-KO. While neither serum levels of autoantibodies norin vitrocytokine responses were affected byNox1deficiency, NOX1 mRNA levels in the spleen significantly increased after the LPS challenge. Among the spleen cells, remarkable LPS-induced upregulation of NOX1 was demonstrated in both CD11b+monocytes/macrophages and CD11c+dendritic cells, suggesting that LPS-inducible NOX1 in monocytes/macrophages/dendritic cells may modulate the development of experimental CIA. Therapeutic targeting of NOX1 may therefore control the onset and/or severity of arthritis which is exacerbated by bacterial infection.