Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen‐induced arthritis

Abstract

Objective. Annexin 1 (Anx-1) is a putative mediator of the antiinflammatory actions of glucocorticoids (GCs). This study investigated the role of Anx-1 in experimental arthritis and in GC-mediated inhibition of inflammation, using antigen-induced arthritis (AIA) in Anx-1 knockout (Anx-1 ؊/؊ ) mice. Methods. Arthritis was induced by intraarticular injection of methylated BSA (mBSA) in mice preimmunized with mBSA. Disease was assessed after 7 days by histologic examination of the knee joints. Serum levels of anti-mBSA IgG were determined by enzyme-linked immunosorbent assay. Cytokine messenger RNA (mRNA) expression was detected by real-time polymerase chain reaction.Results. A significant exacerbation of arthritis was observed in the Anx-1 ؊/؊ mice compared with wild-type (WT) mice. This was associated with increased mRNA expression of synovial interleukin-1␤, tumor necrosis factor ␣, interleukin-6, and macrophage migration inhibitory factor. Dexamethasone significantly reduced the histologic severity of synovitis and bone damage in the WT mice, but exerted no inhibitory effects in the Anx-1 ؊/؊ mice, and also significantly reduced the serum levels of anti-mBSA IgG and the numbers of peripheral blood neutrophils and lymphocytes in WT mice, but had no such effect in Anx-1Conclusion. Anx-1 exerts endogenous antiinflammatory effects on AIA via the regulation of cytokine gene expression, and also mediates the antiinflammatory actions of dexamethasone in AIA.

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

“…Moreover, recent evidences show that Anx-1 exerts endogenous anti-inflammatory effects on adjuvant-induced arthritis via the regulation of cytokine gene expression in the synovium. Endogenous Anx-1 is able to downregulate proinflammatory cytokines, such as IL-1β, TNFα, IL-6, and MIF expression [14]. Thus, it hints that Anx-1 could be one of the promising new agents for treatments specifically tailored to RA, and administration of Anx-1 analogs, or non-GC manipulation of endogenous Anx-1 expression, may be a valuable strategy against arthritis and other inflammatory diseases.…”

Anti-inflammatory functions of glucocorticoid-induced genes

“…Inflammatory responses of an AnxA1 null mouse strain were exaggerated (Chatterjee et al, 2005;Hannon et al, 2003;Warne et al, 2006;Yang et al, 2004), and cells derived from these mice overexpressed COX-2, IL-1β and -6 in response to pro-inflammatory stimuli (Croxtall et al, 2003;Damazo et al, 2006;Hannon et al, 2003;Yang et al, 2006;Yona et al, 2004;Yona et al, 2005), suggesting that AnxA1 is an endogenous inhibitor of inflammatory responses . It should be noted here that cells lacking AnxA1 also showed differences of morphology (Croxtall et al, 2003) and phagocytic properties , which might be indicative of altered membrane physiology.…”

“…It should be noted here that cells lacking AnxA1 also showed differences of morphology (Croxtall et al, 2003) and phagocytic properties , which might be indicative of altered membrane physiology. Importantly, suppressive effects of GCs on carageenininduced oedema, zymosan-induced peritonitis and antigen-induced arthritis were imparied in AnxA1 -/-mice (Hannon et al, 2003;Yang et al, 2004). GCs failed to inhibit the expression of IL-6 and COX-2 in lung fibroblasts lacking AnxA1 (Hannon et al, 2003;Yang et al, 2006).…”

Requirement of phospholipase C‐γ2 (PLCγ2) for Dectin‐1‐induced antigen presentation and induction of TH1/TH17 polarization

“…cDNA was amplified using gene-specific primers for IL-6, TNF-a [45], IL-12p19 [46], EGR-1,-2,-3 [47], IL-2 (5 0 -CAAGCAGGCCACA-GAATTGA and 5 0 -CCGCAGAGGTCCAAGTTCA), COX-2 (5 0 -TGA GTACCGCAAACGCTTCTC and 5 0 -TTTCTTTCTCTCCTGTAAGTTC TTCAA) and hypoxanthine-guanine phosphoribosyl transferase (5 0 -GCAGTACAGCCCCAAAAT and 5 0 -AACAAAGTCTGGCCTG-TATCCAA). Reactions were set up using a iQ SYBR Green Supermix (Bio-Rad, Hercules, CA).…”