Interleukin-32gamma enhances the production of IL-6 and IL-8 in fibroblast-like synoviocytes via Erk1/2 activation.

Introduction: In the present study, we examined the effect of the pro-inflammatory cytokine IL-32gamma, the most biologically active isoform, and its related molecules in fibroblast-like synoviocytes (FLS).

Materials And Methods: FLS were isolated from synovial tissues of rheumatoid arthritis (RA) patients. The secretion and expression of IL-6 and IL-8 were examined by ELISA and real-time PCR, and the activation of signaling molecules was evaluated by Western blot, electrophoretic mobility shift assay (EMSA), real-time PCR, and siRNA transfection.

Results: By IL-32gamma stimulation in RA FLS, the expressions of IL-6 and IL-8 were increased significantly, and the phosphorylated Erk1/2 and AP-1 were expressed prominently in Western blot and EMSA. In the Erk1/2 inhibited cells, IL-32gamma stimulation did not increase the mRNA expression of IL-6 and IL-8.

Conclusion: Our results suggest that IL-32gamma stimulation can induce the production of IL-6 and IL-8 from RA FLS via Erk1/2 activation.