Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response
Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response
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DOI：
10.1016/j.bbrc.2014.09.090
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发表时间：
2014-10-10
影响因子：
3.1
通讯作者：
Son, Youngsook
中科院分区：
文献类型：
--
作者：
Hong, Hyun Sook;Son, Youngsook
目前的类风湿性关节炎（RA）治疗，如生物制剂抑制致病细胞因子基本上延迟RA进展。然而，患者对这些药物的反应并不总是完全和持久的。本研究探讨了P物质（SP），一种11个氨基酸长的内源性神经肽，具有动员间充质干细胞（MSC）和调节损伤介导的炎症的新能力，是否可以抑制RA进展。通过爪肿胀、临床关节炎评分、放射学分析、软骨破坏的组织学分析以及体内肿瘤坏死因子-α（TNF-α）白细胞介素（IL）-10和IL-17的血液水平来评价SP功效。SP治疗显著降低了局部炎症体征、平均关节炎评分、关节软骨降解和炎性细胞侵入滑膜组织。此外，SP治疗显着减少了CIA中过度炎症导致的脾脏增大，增加了IL-10水平，并降低了TNF-α。IL-17水平。SP处理还增加了干细胞的动员以及循环中T-reg和M2型巨噬细胞的诱导。SP的这些作用可能与抑制RA的炎症反应，进而阻断RA的进展有关。我们的研究结果表明，SP作为一种潜在的治疗自身免疫相关的炎症性疾病。(C)由Elsevier Inc.出版。
Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-alpha. and IL-17 levels. Mobilization of stem cells and induction of T-reg and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases. (C) 2014 Published by Elsevier Inc.