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.