Endoplasmic reticulum stress is involved in lipopolysaccharide‐induced inflammatory response and apoptosis in goat endometrial stromal cells

Abstract

Endoplasmic reticulum (ER) stress is involved in regulating cell metabolism, apoptosis, autophagy, and survival. However, there is not enough information about the role of ER stress in lipopolysaccharide (LPS)‐induced apoptosis and inflammatory cytokine secretion in the uterus. In this study, we found that LPS induced apoptosis and inflammation in goat endometrial stromal cells (ESCs). LPS treatment inhibited cell viability and cell proliferation. In addition, the genes associated with proliferation, such as proliferating cell nuclear antigen and MKI67, were affected by LPS treatment. Moreover, LPS increased the secretion of interleukin (IL)‐1β and IL‐8, promoting the levels of MYD88, caspase1, and TRL4. The 4‐phenylbutyric acid pretreatment inhibited the expression of unfolded protein response proteins and the secretion of inflammatory cytokines in LPS‐treated cells. However, blockage of inositol‐requiring enzyme 1 and activating transcription factor 6 did not significantly reduce apoptosis and inflammatory cytokine secretion. Collectively, ER stress involved in LPS‐induced apoptosis and inflammatory cytokine increased in goat ESCs. This study provides new insight into the function of ER stress in the pathological process.

Honokiol inhibits endoplasmic reticulum stress‑associated lipopolysaccharide-induced inflammation and apoptosis in bovine endometrial epithelial cells

“…ER stress has been previously implicated in the LPS-induced apoptosis of endometrial stromal cells and overexpression of inflammatory cytokines in the goat uterus ( 8 ). A close association between ER stress and the activation of thioredoxin-interacting protein/NLR family pyrin domain-containing 3 inflammasome has also been validated in a mouse model of LPS-induced endometritis ( 9 ).…”

“…LPS is considered to be a trigger of the inflammatory response in bEECs in an in vitro endometritis cell model ( 7 ). In addition, previous in vivo and in vitro studies have revealed that endoplasmic reticulum (ER) stress is involved in the inflammatory response and apoptosis of endometrial stromal cells and mouse uterine tissues ( 8 , 9 ).…”

Staphylococcus aureus Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway

“…The UPR sensors mainly include the protein kinase RNA-like endoplasmic reticulum kinase (PERK), the inositol-requiring enzyme (IRE1α), and activating transcription factor 6 (ATF6). Our previous study showed that ER stress was involved in the infection process of multiple pathogens in goat endometrial epithelial cells (gEECs) through different branches, such as LPS, Brucella, and Trueperella pyogenes [8][9][10]. Meanwhile, studies have reported that there is a close relationship between autophagy and the ER stress pathway, or that the two affect each other [11][12][13].…”

UFMylation is associated with LPS‐induced inflammatory response in goat endometrial epithelial cells

“…The UFMylation modification system maintains endoplasmic reticulum homeostasis by regulating the translocation of the nuclear factor kappa B (NF‐κB) protein to the nucleus and stability of inhibitor of NF‐κB (IκB) and inositol‐requiring enzyme 1α (IRE1α), increasing its importance during an inflammatory response (Li et al., 2017; Liu et al., 2017a; Xi et al., 2013). Recent studies indicate that endoplasmic reticulum stress is intimately involved in the occurrence and development of endometritis, an inflammatory disease, and that regulation of endoplasmic reticulum homeostasis reduces its progression, which suggests this could represent a potential target for the prevention and treatment of the disease (Hu et al., 2018; Mohamed et al., 2019; Wu et al., 2018; Yi et al., 2018). Although the pathogenesis of endometritis remains unclear, it has been reported that endoplasmic reticulum stress plays a role in endometritis induced by LPS, and thus, we hypothesize that it may be associated with protein UFMylation (Mohamed et al., 2019).…”

“…Recent studies indicate that endoplasmic reticulum stress is intimately involved in the occurrence and development of endometritis, an inflammatory disease, and that regulation of endoplasmic reticulum homeostasis reduces its progression, which suggests this could represent a potential target for the prevention and treatment of the disease (Hu et al., 2018; Mohamed et al., 2019; Wu et al., 2018; Yi et al., 2018). Although the pathogenesis of endometritis remains unclear, it has been reported that endoplasmic reticulum stress plays a role in endometritis induced by LPS, and thus, we hypothesize that it may be associated with protein UFMylation (Mohamed et al., 2019).…”