Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF- B- and p38 MAPK-dependent signalling pathways

Abstract

IL-23p19 is over-expressed in RA synovial fibroblasts and IL-17 appears to up-regulate the expression of IL-23p19 in RA synovial fibroblasts via PI3-kinase/Akt, NF-kappaB- and p38-MAPK-mediated pathways. These results suggest that a disruption of interaction between IL-17 and IL-23p19 may provide a new therapeutic approach in the treatment of RA.

Gamma/delta T cells are the predominant source of interleukin‐17 in affected joints in collagen‐induced arthritis, but not in rheumatoid arthritis

“…Furthermore, IL-17-producing ␥/␦ T cells were induced equivalently in response to stimulation by IFA plus solution in the absence of type II collagen. Together with results from the previous study demonstrating that IL-17-producing ␥/␦ T cells are induced equally by CFA plus type II collagen and CFA (16), the present data suggest that IL-17-producing ␥/␦ T cells do not recognize the specific antigen (type II collagen) but rather proliferate in response to IL-23, which may be produced locally by synovial cells (44). The ligands of ␥/␦ T cells are largely unknown, and further analysis of possible antigens of IL-17-producing ␥/␦ T cells in CIA could be difficult (47).…”

“…Here, it was demonstrated that the combination of IL-23 and IL-1␤ synergistically stimulated IL-17 production, but stimulation via ␥/␦ TCR had a limited effect. Given the enhanced expression of IL-1␤ and IL-23 in the inflamed joints of mice with CIA (44,45), these findings suggest that IL-17 production by ␥/␦ T cells in CIA might mainly be an inflammatory cytokine-driven process rather than a TCR signal-driven process.…”

Interleukin‐17 in fashion, at last: Ten years after its description, its cellular source has been identified

“…Research is also ongoing on small molecules that are able to control the intracellular signaling pathways to interfere specifically with IL-17-induced cell activation or, less specifically, act on TNF and IL-1 pathways. Currently, an IL-17-specific signaling pathway has not been identified in synoviocytes (34). Conversely, suppressor of cytokine signaling 3 is an essential negative regulator of IL-23 signaling, and then of IL-17 production (35).…”

Pathogenic Role of Interlukin-23(IL-23) in Rheumatoid Arthritis Patients; its Relation to Disease Activity

“…Kim et al revealed that IL-23p19 is over-expressed in RA synovial fibroblasts and IL-17 appears to up-regulate the expression of IL23p19 in RA synovial fibroblasts. 22 The concentration of IL-23p19 correlated with the concentration of IL-17 in synovial fluid and sera of RA patients. They concluded that upregulated IL-23p19 in synovial fluid might be involved in joint destruction in RA through interplay with IL-17.…”