IL-34 regulates MAPKs, PI3K/Akt, JAK and NF-?B pathways and induces the expression of inflammatory factors in RA-FLS
Clinical and experimental rheumatology(2022)
Abstract
Objective To explore the role of interleukin 34 (IL-34) in rheumatoid arthritis (RA) and its related signalling pathways as well as the expression levels of IL-34 in collagen-induced arthritis (CIA) modelling mice. Methods Recombination IL-34 was used to stimulate cultured RA fibroblast-like synoviocytes (RA-FLS). The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA), and the levels of phosphorylation signalling molecules were detected by western blotting assay (WB). After the establishment of the CIA model, paw indexes and serum IL-34 expression levels of mice were evaluated. Results IL-34 significantly increased the secretion of IL-8 and TNF-alpha but had no significant effect on IL-6, and this effect could be impaired by signal inhibitors. At the same time, IL-34 activated multiple signaling pathways, whereas treating with inhibitors could reduce phosphorylation intensity. In animal experiments, mice in the model group had lost weight, and their paws were obviously swollen, ulcerous, and even stiffened. The hyperplasia of synovial tissue, infiltration of many inflammatory cells, and destruction of bone and cartilage from the typical pannus formation were also apparently observed. Conclusion IL-34 can mediate the production and secretion of IL-8 and TNF-alpha in RA-FLS cells through MAPKs, PI3K/Akt, JAK and NF-kappa B signalling pathways, while the expression of serum IL-34 in collagen-induced arthritis mice is also upregulated.
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Key words
Key rheumatoid arthritis,interleukin 34,signalling pathways,collagen-induced arthritis
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