Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation.

Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation.
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DOI:
10.1155/2017/9832430
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发表时间:
2017
影响因子:
4.1
通讯作者:
Takaso M
Takaso M
中科院分区:
医学3区
文献类型:
--
作者:
Takano S;Uchida K;Miyagi M;Inoue G;Aikawa J;Iwabuchi K;Takaso M

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肾上腺髓质素(adrenomedullin,AM)在炎症过程中起着重要的调节作用,但其在滑膜炎症中的作用和表达尚不清楚。为探讨AM在炎症滑膜组织(ST)中的表达及其作用,采用小鼠膝关节手术脱位模型,研究了AM在滑膜巨噬细胞和成纤维细胞中的基因表达。此外,还检测了IL-1β和AM对培养的滑膜细胞的影响。CD11c+巨噬细胞在手术脱位的膝盖骨中明显升高。脱位侧ST段CD11c、IL-1β、AM、受体活性修饰蛋白2(RAMP2)和RAMP3(RAMP3)的基因表达水平也较高。IL-1β处理后,滑膜成纤维细胞和巨噬细胞AM的表达也显著增加。与成纤维细胞相比,滑膜巨噬细胞也高表达RAMP3,这种表达被外源性添加的IL-1β进一步刺激。此外,用AM处理ST中F4/80阳性细胞组分可抑制IL-1β的表达。综上所述,这些结果表明炎症ST中AM是由滑膜成纤维细胞和巨噬细胞产生的,AM水平升高可能对滑膜巨噬细胞起到抗炎作用。
Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages.
DOI: 10.1186/ar2550
发表时间: 2008
影响因子: 4.9
作者:
Okura T;Marutsuka K;Hamada H;Sekimoto T;Fukushima T;Asada Y;Kitamura K;Chosa E
通讯作者: Chosa E