IL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth

- Aberrant expression of IL-27 in peripheral serum and its specific receptor wsx-1 in preterm birth women are observed.
- IL-27 enhances the release of IL-1β, IL-6, TNF-α, IFN-γ, CXCL10 and MCP-1 in human fetal membranes.
- IL-27 amplifies the expression of CXCL10 in synergy with IFN-γ in human fetal membranes.
- Molecular inhibitors of c-JNK, PI3K and/or Erk signaling pathways attenuates production of CXCL10 in IL-27-treated fetal membrane.
- IL-27 activates MMP2 and MMP9 in human fetal membranes.
- IL-27 may play a potential role in predicting preterm birth.

Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-fetal interface that would mediate the onset of preterm birth. We found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN-γ, MCP-1, IL-6, IL-1β and TNF-α), especially CXCL10, was markedly augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27 and IFN-γ cooperated to amplify the expression of CXCL10 in the fetal membranes. Moreover, the production of CXCL10 was increased in IL-27-treated fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and MMP9 were activated by IL-27 in human fetal membranes, which may be related to the onset of preterm premature rupture of membranes (pPROM). In conclusion, for the first time, we reported that the aberrant expression of IL-27 could mediate an excessive inflammatory response in fetal membranes through the JNK, PI3K or Erk signaling pathways, which contributes to preterm birth.