Impaired pathogen-induced autophagy and increased IL-1β and TNFα release in response to pathogenic triggers in secretory phase endometrial stromal cells of endometriosis patients.

RESEARCH QUESTION:It is not clear whether innate immunity along with autophagy is altered in endometrial cells of patients with endometriosis. DESIGN:This study evaluated the effects of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) stimulation on autophagy induction, pro-IL-1β expression, and secretion of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNFα) in endometrial epithelial and/or stromal cells of patients with endometriosis (EE-endo, ES-endo, respectively), those of patients with hydrosalpinx (EE-hydro, ES-hydro, respectively) and those of healthy fertile women (EE-healthy, ES-healthy, respectively), with and without inhibition of autophagy by autophagy-related (ATG)13 gene small interfering RNA (siRNA). RESULTS:Stimulation with either LPS or poly I:C triggered autophagy in EE/ES-healthy, whereas no significant induction was observed in either EE/ES-endo or EE/ES-hydro. In EE- and/or ES-healthy, IL-1β and/or TNFα secretion after stimulation with LPS or poly I:C was significantly higher in cells with ATG13 knockdown compared with those with siRNA control (P < 0.03), whereas no significant difference was observed in either EE/ES-endo or EE/ES-hydro. In the secretory phase ES-endo without autophagy inhibition, IL-1β and TNFα secretion were significantly higher compared with those of ES-healthy after stimulation with either LPS or poly I:C for 4 h (P < 0.001) and for 24 h (P < 0.01). CONCLUSION:Pathogen-induced autophagy was impaired in EE/ES-endo. Increased IL-1β and TNFα release in response to pathogenic triggers in the secretory phase ES-endo may result in the development of an inflammatory uterine microenvironment detrimental to successful embryo implantation.