Stimulatory Effect of LPS and Feedback Effect of PGE2 on IL‐27 production

Interleukin (IL)‐27 is a new member of the IL‐6/IL‐12 family, composed of two subunits, the Epstein-Barr virus-induced gene 3 (EBI3) and p28 chains (p28), and produced by activated monocytes and dendritic cells. IL‐27 plays an important role in the regulation of differentiation of naive T helper cells and has diverse effects on innate immune cells. However, the pro‐inflammatory mechanisms of IL‐27 are still not well known. In this study, we investigated the effect of lipopolysaccharide (LPS) on the production of IL‐27. We found that LPS‐stimulated IL‐27 production was in a dose‐dependent and time‐dependent manner in THP‐1 cells. We have also shown that IL‐27 induced PGE2 production and COX‐2 gene expression at the level of mRNA as well as protein. Moreover, we found feed back effect of PGE2 on the production of IL‐27 in THP‐1 cells. The results suggest that PGE2 significantly inhibits LPS‐induced IL‐27 production, without affecting basal IL‐27 expression. Further experiment suggests that PGE2 and LPS regulate IL‐27 through NF‐κB pathway. Our findings may have wide implication for IL‐27 in inflammatory diseases.