Impact of the Reticular Stress and Unfolded Protein Response on the inflammatory response in endometrial stromal cells

GRASSO, E. *; GORI S. * (CONTRIBUCION IDENTICA); SOCZEWSKI, E.; FERNÁNDEZ, L.; GALLINO, L.; VOTA, D.; MARTÍNEZ, G.; IRIGOYEN, M.; RUHLMANN, C.; LOBO, T. F.; SALAMONE, G.; MATTAR, R.; DAHER, S.; RAMHORST, R.

Scientific Reports

Nature

Lugar: Amsterdam; Año: 2018 vol. 8

During decidualization, endometrial stromal cells undergo reticular stress (RS) and unfolded proteinresponse (UPR), allowing the endoplasmic reticulum-expansion and immunomodulators production.Physiological RS generates the activation of sensing proteins, inflammasome activation and matureIL-1β secretion, associated with pro-implantatory effects. We focus on the impact of RS and UPR ondecidualized cells and whether they induce a physiological sterile inflammatory response throughIL-1β production. Human endometrial stromal cell line (HESC) after decidualization treatment withMPA + dibutyryl-cAMP (Dec) increased the expression of RS-sensors (ATF6, PERK and IRE1α) andUPR markers (sXBP1 and CHOP) in comparison with Non-dec cells. Then we found increased NLRP3expression in Dec cells compared with Non-dec cells. In fact STF-083010 (an IRE1α inhibitor) preventethis increase. Downstream, increased levels of active caspase-1 on Dec cells were detected by FAM-FliCaspase-1 associated with an increase in IL-1β production. Moreover, the treatment with STF-083010decreased the invasion index observed in Dec cells, evaluated by an in vitro model of implantation. Inendometrial biopsies from recurrent spontaneous abortion patients an increased expression of IRE1αwas found in comparison with fertile women; while recurrent implantation failure samples showeda lower expression of sXBP1, TXNIP and NLRP3 than fertile women, suggesting that RS/UPR tenorsmight condition endometrial receptivity