The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy

Abstract

The purpose of this study was to analyze the expression of the two proinflammatory cytokines IL-20 and IL-24 and their shared receptors in rheumatoid arthritis and spondyloarthropathy. IL-20 was increased in plasma of rheumatoid arthritis patients compared with osteoarthritis patients and IL-24 was increased in synovial fluid and plasma of rheumatoid arthritis and spondyloarthropathy patients compared with osteoarthritis patients. IL-20 and IL-24 mRNA was only present at low levels in the synovium. In the synovial membrane, IL-20 protein was present in mononuclear cells and neutrophil granulocytes whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL-20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with recombinant human IL-20 or recombinant human IL-24 induced monocyte chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid arthritis and spondyloarthropathy and results indicate that the two cytokines contribute to disease pathogenesis through recruitment of neutrophil granulocytes and induction of CCL2/MCP-1.

Stat6 and c-Jun Mediate Th2 Cell-Specific IL-24 Gene Expression

“…IL-24 is produced not only by activated immune cells but also to a similar extent by nonimmune cells such as cultured melanocytes (10), dermal keratinocytes (17), and IL-1-stimulated human colonic subepithelial myofibroblasts (18). IL-24 expression also has been reported in affected joints of rheumatoid arthritis patients (19) and is involved in the immunopathology of psoriasis (17,20) at the edge of excisional skin wounds (21) and in active lesions from patients who have ulcerative colitis and Crohn's disease (18). IL-24 inhibits differentiation of germinal center B cells into mature plasma cells and promotes their maturation toward the memory B cell pathway (22).…”

Interleukin-10 Superfamily and Cancer

“…Binding of IL-20 to its corresponding complexes causes elevated proinflammatory activity in mesangial cells, keratinocytes, endothelial cells, synovial fibroblasts, and renal epithelial cells (Blumberg et al, 2001;Otkjaer et al, 2007). An inflammatory-promoting activity of IL-20 was found to be markedly associated with features of development and pathogenesis of various diseases and conditions (Hofmann et al, 2012), including those of rheumatoid arthritis (Hsu et al, 2006;Kragstrup et al, 2008;Hsu and Chang, 2010), atherosclerosis (Caligiuri et al, 2006;Chen et al, 2006;Kleemann et al, 2008), psoriasis (Wei et al, 2005;Sa et al, 2007;Wang et al, 2012b), brain injury (Chen and Chang, 2009), ulcerative colitis (Fonseca-Camarillo et al, 2013), and renal failure (Li et al, 2008a). In addition, IL-20 overexpression in transgenic mice resulted in neonatal lethality with skin abnormalities including aberrant epidermal differentiation (Blumberg et al, 2001).…”

Involvement of soluble receptor activator of nuclear factor-κB ligand (sRANKL) in collagenase-induced murine osteoarthritis and human osteoarthritis

“…It has been demonstrated that the complement receptors CR1, CR3, and CR4 are up-regulated in RA neutrophils [17] simultaneously with enhanced peripheral degranulation, superoxide anion generation, and increased chemotaxis to synovium [18]. Neutrophil recruitment is promoted by TNF-a, IL-17, IL-20, and IL-24, all with impact on bone turnover [19,20]. Recently, Poubelle and co-workers reported that RA neutrophils express RANKL and are activated through RANK/RANKL interaction [21].…”