IL-1 β Inhibits Connexin 43 and Disrupts Decidualization of Human Endometrial Stromal Cells through ERK1/2 and p38 MAP Kinase.

We examined how IL-1β affects expression of the uterine gap junction protein, Cx43, which is known to be critical for embryonic implantation. We used an in vitro model of human endometrial stromal cells (ESC), Western blotting and a combination of validated, selective kinase inhibitors to evaluate five canonical IL-1β signaling pathways. Cx43 and two other markers of ESC differentiation (prolactin and VEGF) were inhibited predominantly via IL-1β-activated ERK1/2 and p38 MAP kinase cascades. The findings were corroborated using siRNA to silence critical genes in either pathway. By contrast, upregulation of endogenous pro-IL-1α and -IL-1β following recombinant IL-1β treatment was mediated via the Jun N-terminal Kinase (JNK) pathway. The clinicopharmacological significance of our findings is that multiple signaling cascades may need to be neutralized to reverse deleterious effects of IL-1β on human endometrial function.
PMID: 28938400 [PubMed - as supplied by publisher]

Source: Endocrinology - September 11, 2017 Category: Endocrinology Authors: Yu J, Berga SL, Zou W, Yook DG, Pan JC, Andrade AA, Zhao L, Sidell N, Bagchi IC, Bagchi MK, Taylor RN Tags: Endocrinology Source Type: research