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

Abstract

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.

Prostaglandin E2 Inhibition of IL-27 Production in Murine Dendritic Cells: A Novel Mechanism That Involves IRF1

“…Previously, we reported that PGE2 inhibited IL-27 expression in BMDCs (34), and Zhu et al (35) reported similar results in THP-1 cells. Here we report that PGE2 inhibition of IL-27 is similar in BMDCs, BMDMs, and splenic DCs, and that it occurs upon activation of various TLRs.…”

“…Although the mechanisms involved in the induction of IL-27 in cDCs and macrophages have been studied extensively, little is known about factors and mechanisms that negatively impact IL-27 expression. We were the first to report that PGE2 inhibited IL-27 production by BMDCs (56), and a later publication reported on a similar finding in THP-1 cells (35). Here we report that PGE2 inhibits IL-27 production and p28 expression through a novel mechanism involving EP2/EP4-mediated cAMP increase, subsequent inhibition of irf1 expression and reduced IRF1 binding to the p28 promoter ISRE site.…”

“…To date, little is known about the interaction between PGE2 and IL-27. Two publications, including one from our laboratory, reported previously that PGE2 inhibited LPS-induced IL-27p28 expression in BMDC (34) and THP-1 cells (35). In the present study we report that PGE2 inhibits IL-27 expression in bone marrow-derived DC (BMDC) and macrophages (BMDM), and in splenic DCs in vitro and in vivo.…”

Roles of prostaglandin E2 in the cochlea

“…Studies on knock-out mice deficient for individual EPs clearly revealed that PGE2 not only acts as a pro-inflammatory mediator, but also exerts anti-inflammatory responses (Sugimoto and Narumiya, 2007). In addition, recent investigations have demonstrated significant roles of PGE2 signaling, in particular EP2 and EP4 signaling, in innate and adaptive immune systems (Divangahi et al, 2010;Gagliardi et al, 2010;Mandapathil et al, 2010;Zhu et al, 2010). PGE2 is classically known as an immunosuppressant, because it inhibits helper T cell differentiation (Harris et al, 2002;Sugimoto and Narumiya, 2007).…”

Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease

“…However, the ginger extract may directly and/or indirectly influence the IL-27 production. For example, it has been reported that PGE2 (a production of COX-2) significantly inhibits LPS-induced IL-27 production by monocytic cell line (Zhu et al, 2010). On the other hand, the inhibitory effects of the ginger extract on the COX-2 have been demonstrated (Choi et al, 2013a).…”