The Role of α-Enolase on the Production of Interleukin (IL)-32 in Con A-Mediated Inflammation and Rheumatoid Arthritis (RA).

ABSTRACT

Interleukin (IL)-32 is produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. IL-32 induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1ß, IL-6, and IL-8, and IL-32 expression is highly increased in rheumatoid arthritis (RA) patients. Enolase-1 (ENO1) is a glycolytic enzyme and the stimulation of ENO1 induces high levels of pro-inflammatory cytokines in concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and macrophages in RA patients. In addition, there are many reports that anti-ENO1 antibody is correlated with the disease progression of RA. It implies that ENO1 could regulate IL-32 production during inflammation related to the pathogenesis of RA. Therefore, we investigated the role of ENO1 in IL-32 production using Con A-activated PBMCs and RA PBMCs. IL-32 expression is increased by ENO1 stimulation using real-time PCR and ELISA. In addition, we confirmed that IL-32 production was decreased in Con A-activated PBMCs and RA PBMCs pre-treated with NF-κB or p38 MAPK pathway inhibitors. Taken together, these results suggest that ENO1 plays an important role in inflammation through the induction of IL-32 production by the activation of the NF-κB and p38 MAPK pathways.