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气体6/Axl轴激活减轻了骨关节炎纤维细胞样同胞细胞和同胞突破体中的炎症反应

Juliana P Vago¹, Natália Valdrighi¹, Esmeralda N Blaney-Davidson¹

¹Experimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Pharmaceuticals (Basel, Switzerland)

|May 27, 2023

概括

增长停止特异性基因6 (Gas6) 通过激活TAM受体来减少骨关节炎的炎症. 这项研究表明,Gas6可以抑制患者细胞和组织中的关键炎症标志物.

科学领域:

免疫学免疫学免疫学
类风湿病学类风湿病学
细胞生物学细胞生物学

背景情况:

骨关节炎 (OA) 是一种普遍的关节疾病,其特点是软骨退化和炎症.
TAM受体 (Tyro3, Axl, Mer) 对于免疫调节和组织修复至关重要.
增长停止特异性基因6 (Gas6) 是TAM受体的配体,但其在OA炎症中的作用尚不清楚.

研究的目的:

研究Gas6对骨关节炎患者的突纤维细胞和突细胞的抗炎作用.
阐明涉及TAM受体信号传递的潜在分子机制.

主要方法:

评估TAM受体表达和Gas6和可溶性Axl (sAxl) 在OA突液和细胞中的水平.
在炎症刺激 (LPS) 下,用气6条件介质 (Gas6-CM) 处理的OA纤维细胞状同胞细胞 (OAFLS) 和同胞突破体.
使用TAM受体的药理抑制剂 (RU301,RU428) 并分析下游信号通路 (STAT,SOCS).

主要成果:

在炎症下,OA突液的sAxl高于Gas6;在炎症下,OAFLS的sAxl增加,Gas6降低.
在OAFLS和IL-6,CCL2,IL-1β中,Gas6-CM显著降低了OA突发炎的促炎标志物 (IL-6,TNF-α,IL-1β,CCL2,CXCL8). 在OA突发炎的突发炎突发体中,IL-6,CCL2,IL-1β显著降低了OA突发炎的促炎标志物.
Gas6的抗炎作用依赖于轴激活,导致STAT1/STAT3酸化和SOCS1/SOCS3诱导.

结论:

气体6治疗有效地抑制了骨关节炎患者衍生的细胞和组织中的炎症标志物.
在OA中Gas6的抗炎作用通过轴激活和随后的SOCS1/3产生.
气体6代表了一种潜在的治疗点,用于治疗骨关节炎的炎症.

关键词:

气体6 是一个气体.这种TAM受体是TAM受体.骨关节炎是一种关节炎.综合性炎症综合性炎症

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