Abstract
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.
Highlights
The synovial membrane lines the cavity of synovial joints and is composed of macrophage- and fibroblast-like synoviocytes and an underlying layer of synovial tissue
In the present study investigating the role of AM in synovial inflammation, CD11c+ populations of macrophages were found to be elevated in the synovial tissue (ST) of a murine patellar surgical dislocation model
Higher gene expression of the genes encoding CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and RAMP3 was observed in ST from the dislocated side compared to control ST
Summary
The synovial membrane lines the cavity of synovial joints and is composed of macrophage- and fibroblast-like synoviocytes and an underlying layer of synovial tissue. Synovial macrophages produce several inflammatory cytokines, including interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α, which contribute to arthritis progression and associated joint pain [1,2,3]. For this reason, the regulation factor of these cytokines in synovial tissue (ST) may aid in the understanding of arthritis pathogenesis and synovial inflammation. AM belongs to the calcitonin gene-related peptide (CGRP) family and was originally identified in human pheochromocytoma tissue using elevated platelet cAMP activity as an indicator [6]. The role and expression of AM in synovial inflammation have not been determined
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