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

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

Scientific Reports

SPRINGER NATURE

Año: 2018 vol. 8

During decidualization, endometrial stromal cells undergo reticular stress (RS) and unfolded protein response (UPR), allowing the endoplasmic reticulum-expansion and immunomodulators production. Physiological RS generates the activation of sensing proteins, inflammasome activation and mature-IL-1β secretion, associated with pro-implantatory effects. We focus on the impact of RS and UPR on decidualized cells and whether they induce a physiological sterile inflammatory response through IL-1β production. Human endometrial stromal cell line (HESC) after decidualization treatment with MPA+cAMP (Dec) increased the expression of RS-sensors (ATF6, PERK and IRE1α) and UPR markers (sXBP1 and CHOP) in comparison with Non-dec cells. Then we found increased NLRP3 expression in Dec cells compared with Non-dec cells. inIn fact STF-083010 (an IRE1α- inhibitor) prevented this increase. Downstream, increased levels of active caspase-1 on Dec cells were detected by FAM-Flica Caspase-1 associated with an increases in IL-1β production. Moreover, the STF-083010-treatment decreased the invasion index observed in Dec cells, evaluated by an in vitro model of implantation. In endometrial biopsies from recurrent spontaneous abortions-patients an increase expression of IRE1α, sXBP1, TXNIP, NLRP3 and IL-1β was found in comparison with fertile women; while recurrent implantation failures samples showed a lower expression than fertile women, suggesting that RS/UPR tenors might condition endometrial receptivity. E. Grasso and S. Gori contributed equally to this work.