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Inflammation plays a pivotal role in the terminal process of human labor and delivery, including myometrial contractions and membrane rupture. TNF-alpha-induced protein 8-like-2 (TIPE2) is a novel inammation regulator; however, there are no studies on the role of TIPE2 in human labor. We report that in myometrium, there is decreased  TIPE2  mRNA expression during late gestation which was further decreased in labor. In fetal membranes,  TIPE2  mRNA expression was decreased with both term and preterm labor compared to no labor samples. Knockdown of TIPE2 by siRNA in primary myometrium and amnion cells was associated with an augmentation of IL1B and TNF-induced expression of pro-inflammatory cytokines and chemokines; expression of contraction-associated proteins and secretion of the uterotonic prostaglandin PGF 2α  and expression of extracellular matrix degrading enzymes. In TIPE2-deficient myometrial cells treated with inhibitors of NF-κB or ERK1/2, the secretion of pro-labor mediators was reduced back to control levels. In conclusion, these  in vitro  experiments indicate that loss of TIPE2 exacerbates the inflammatory response.

Novel anti-inflammatory actions of TIPE2 in human primary amnion and myometrial cells