IL‑1β increases the expression of inflammatory factors in synovial fluid‑derived fibroblast‑like synoviocytes via activation of the NF‑κB‑mediated ERK‑STAT1 signaling pathway.

Abstract

Interleukin (IL)-1β serves a crucial role in the progression of rheumatoid arthritis. Previous studies have indicated that the ERK/STAT1 signaling pathway may be involved in the inflammatory response in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs). However, the molecular mechanisms underlying the pathological effects of the inflammatory factors induced by IL-1β in sfd-FLSs remain unclear. The aim of the present study was to investigate the IL-1β-mediated signaling pathways involved in the expression of inflammatory factors in sfd-FLSs and in a rat model of rheumatoid arthritis. Reverse transcription-quantitative PCR, western blotting, and immunohistochemistry were used to analyze the role of IL-1β in the rat model of rheumatoid arthritis. The results suggested that IL-1β administration exacerbated rheumatoid arthritis, bone injury and increased the expression levels of inflammatory factors, such as IL-17 and tumor necrosis factor α (TNF-α), whereas treatment with anti-IL-1β exhibited opposite effects. In vitro experiments in sfd-FLSs further suggested that treatment with IL-1β influenced the expression levels of various inflammatory factors. In specific, IL-1β increased the expression of IL-17 and TNF-α, and decreased the expression of IL-6 and IL-10 in sfd-FLSs. Additionally, treatment with IL-1β increased the mRNA expression and protein phosphorylation of NF-κB, ERK and STAT1 in sfd-FLSs. Treatment with anti-IL-1β exhibited opposite effects on the expression levels of inflammatory factors and suppressed the NF-κB-mediated ERK-STAT1 signaling pathway activation in sfd-FLSs. Finally, treatment with a NF-κB inhibitor suppressed the effects of IL-1β, and NF-κB overexpression reversed the effects of anti-IL-1β on the expression levels of IL-17, TNF-α, NF-κB, ERK and STAT1. In conclusion, the present results demonstrated that treatment with IL-1β increased the expression levels of inflammatory factors in sfd-FLSs via the regulation of the NF-κB-mediated ERK/STAT1 signaling pathway in a rat model of rheumatoid arthritis. Therefore, the NF-κB/ERK/STAT1 signaling pathway may represent a potential target for the development of novel treatments for rheumatoid arthritis.