Losartan suppresses the inflammatory response in collagen-induced arthritis by inhibiting the MAPK and NF-κB pathways in B and T cells
Losartan suppresses the inflammatory response in collagen-induced arthritis by inhibiting the MAPK and NF-κB pathways in B and T cells
复制标题
氯沙坦通过抑制 B 细胞和 T 细胞中的 MAPK 和 NF-κB 通路来抑制胶原诱导的关节炎的炎症反应
DOI：
10.1007/s10787-018-0545-2
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发表时间：
2018-11
影响因子：
5.8
通讯作者：
Wei Wei
中科院分区：
文献类型：
--
作者：
Xinming Wang;Xiaoyun Chen;Wei Huang;Pengying Zhang;Yawei Guo;Heinrich Körner;Huaxun Wu;Wei Wei
血管紧张素II 1型受体（AT 1 R）拮抗剂氯沙坦已被证实在体外和体内具有中度抗炎作用。然而，它如何影响风湿性关节炎（RA）的免疫细胞仍然是未知的。我们发现，在人类滑膜组织中，AT 1 R在T细胞和B细胞上显著表达。氯沙坦（15 mg/kg）单独治疗和与低剂量甲氨蝶呤（MTX 0.25 mg/kg/3天）联合治疗可显著抑制CIA的进展。治疗后继发性足肿胀、关节破坏和血清中促炎细胞因子（TNF-α和IFN-γ）的存在减轻。氯沙坦的治疗作用是基于减少T细胞和B细胞活化，特别是通过减少细胞活力和促炎细胞因子的产生。此外，氯沙坦与小剂量MTX联合使用也可达到相似的治疗效果，同时保护肝脏和肾脏免受MTX的损害。在机制上，氯沙坦抑制促炎介质的产生，减少T细胞和B细胞中p38、ERK和p65、p50核转位的磷酸化。在CIA大鼠模型中，氯沙坦不影响JNK的磷酸化。氯沙坦可能通过下调p38、ERK的磷酸化和NF-κB的信号传导而发挥抗关节炎作用。在达到类似的抗风湿作用的同时，氯沙坦与低剂量MTX的联合治疗可以保护由给予高剂量MTX引起的肝和肾损伤。
The angiotensin II type 1 receptor (AT1R) antagonist losartan has been confirmed to have a moderate anti-inflammatory effect in vitro and in vivo. However, how it affects immune cells in Rheumatoid Arthritis (RA) is still unknown. We found that in human synovial tissues, AT1R is significantly expressed on T cells and B cells. Treatment with losartan (15 mg/kg) alone and in combination with a low dose of methotrexate (MTX 0.25 mg/kg/3 days) significantly suppressed the progression of CIA. Secondary paw swelling, joint destruction and the presence of pro-inflammatory cytokines (TNF-α and IFN-γ) in the serum were alleviated after treatment. The therapeutic effects of losartan were based on reduced T-cell and B-cell activation, specifically by decreased cell vitality and pro-inflammatory cytokine production. In addition, losartan combined with a low dose of MTX achieved a similar therapeutic effect, while protecting liver and kidney from MTX damage. Mechanistically, losartan inhibits the production of pro-inflammatory mediators, reduces the phosphorylation of p38, ERK, and p65, p50 nuclear transposition in T cells and B cells. Phosphorylation of JNK is not affected by losartan in the CIA rat model. losartan can be used as an effective RA treatment, which exhibits anti-arthritic effects potentially through down-regulating the phosphorylation of p38, ERK and signaling through NF-κB. While achieving similar anti-rheumatic effects, a combination therapy of losartan with a low dose of MTX, can protect from liver and renal damage caused by giving a high dose of MTX.
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影响因子：
3.2
作者：
Pala O;Diaz A;Blomberg BB;Frasca D
通讯作者：
Frasca D
OX40L通过PI3K/AKT和P38 MAPK信号通路诱导哮喘细胞免疫过程中辅助T细胞分化
影响因子：
7.4
作者：
Huang L;Wang M;Yan Y;Gu W;Zhang X;Tan J;Sun H;Ji W;Chen Z
通讯作者：
Chen Z
影响因子：
4.6
作者：
Wang Q;Wang L;Wu L;Zhang M;Hu S;Wang R;Han Y;Wu Y;Zhang L;Wang X;Sun W;Wei W
通讯作者：
Wei W
影响因子：
1.6
作者：
Ohkura Y;Shindoh J;Haruta S;Kaji D;Ota Y;Fujii T;Hashimoto M;Watanabe G;Matsuda M
通讯作者：
Matsuda M
影响因子：
37.8
作者：
Kvakan, Heda;Kleinewietfeld, Markus;Muller, Dominik N.
通讯作者：
Muller, Dominik N.