ISGylation Inhibits an LPS-Induced Inflammatory Response via the TLR4/NF-κB Signaling Pathway in Goat Endometrial Epithelial Cells

Endometritis is a common and important reproductive disease of domestic animals. The principal factors responsible for the disease are infection with Gram-negative bacteria, the release of Lipopolysaccharides (LPS) and activation of the TLR4/NF-kappa B signaling pathway. However, we do not fully understand the interaction between endometrial immunity and bacterial infection in the disease etiology. The ubiquitin-like protein ISG15 can regulate the TLR4/NF-kappa B signaling pathway via the ISGylation modification system, modulating the inflammatory response. In the present study, we found that ISG15 protein was expressed mainly in the cytoplasm of goat endometrial epithelial cells (gEECs) and that the expression of key genes and proteins of ISGylation increased in LPS-induced gEECs. Overexpression and silencing of the ISG15 gene demonstrated that ISGylation inhibited an LPS-induced inflammatory response via the TLR4/NF-kappa B signaling pathway in gEECs. Here, we provide the experimental basis for further exploration of the role of the ISGylation modification system in the inflammatory response of endometrium and a potential method for the treatment of endometritis.

Automated summary

Endometritis is a common reproductive disease in domestic animals caused by Gram-negative bacterial infection, where the ISGylation modification system can regulate the inflammatory response by modulating the TLR4/NF-kappa B signaling pathway. Experimental evidence shows that ISG15 can inhibit LPS-induced inflammatory response through ISGylation.