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

作者:Takano Shotaro; Uchida Kentaro; Miyagi Masayuki; Inoue Gen; Aikawa Jun; Iwabuchi Kazuya; Takaso Andmasashi
来源:Journal of Immunology Research, 2017, 2017: 9832430.
DOI:10.1155/2017/9832430

摘要

<jats:p>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-<jats:italic>(IL-) 1<jats:italic>β</jats:italic></jats:italic>and AM in cultured synovial cells were also examined. CD11c<jats:sup>+</jats:sup>macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of<jats:italic>CD11c</jats:italic>,<jats:italic>IL-1<jats:italic>β</jats:italic></jats:italic>,<jats:italic>AM</jats:italic>, receptor activity-modifying proteins 2<jats:italic>(RAMP2)</jats:italic>, and 3<jats:italic>(RAMP3)</jats:italic>was also observed in ST obtained from the dislocated side.<jats:italic>AM</jats:italic>expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1<jats:italic>β</jats:italic>treatment. Synovial macrophages also highly expressed<jats:italic>RAMP3</jats:italic>compared to fibroblasts and this expression was further stimulated by exogenously added IL-1<jats:italic>β</jats:italic>. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited<jats:italic>IL-1<jats:italic>β</jats:italic></jats:italic>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.</jats:p>

  • 出版日期2017