MiR-424-5p overexpression inhibits LPS-stimulated inflammatory response in bovine endometrial epithelial cells by targeting IRAK2. (March 2022)

• Record Type: Journal Article
• Authors: Umar, Talha; Ma, Xiaofei; Yin, Baoyi; Umer, Saqib; Zahoor, Arshad; Akhtar, Muhammad; Umar, Zaima; Shaukat, Aftab; Deng, Ganzhen
• Is Part Of: Journal of reproductive immunology. Volume 150(2022)
• Publication Date: 2022-03
• Subjects: NF‐κB -- miR-424-5p -- IRAK2 -- Endometritis -- Lipopolysaccharides; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2021.103471
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: miR-424-5p serves as an inhibitor in the immune inflammatory response via targeting NF-κB pathway in LPS-primed endometritis. miR-424-5p mitigates the inflammation process in BEECs and could inhibit the activation of the LPS-primed NF-κB pathway. Inhibition of NF-κB could be a potential molecular target for endometritis treatment in the future. Abstract: Endometritis is inflammation of endometrium due to various factors and is a common cause of infertility. Several remedies used for endometritis like antibiotics, hormones, and herbs. Studies confirm that microRNAs play a significant role in various inflammatory diseases. However, the role of miR-424-5p in endometritis is not clear. In our study, histopathology, real‐time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence, ELISA, and dual-luciferase reporter assay were used to elucidate the effect of miR‐424-5p in lipopolysaccharide (LPS)‐primed inflammatory response in bovine endometrial epithelial cells (BEECs) and clarify the potential mechanism. Our results revealed that miR-424-5p mimics noticeably decrease the production of proinflammatory cytokines (IL‐1β, IL-6, and TNF‐α), while miR-424-5p inhibitors have inverse effects in BEECs. Moreover, overexpression of miR‐424-5p on BEECs cells also suppressed NF‐κB p65 activation. Afterwards, we verified that miR‐424-5p inhibited Interleukin 1 Receptor Associated Kinase 2 (IRAK2) expression by binding to the 3′‐UTR of IRAK2 mRNA. Further, co-transfection of miR-424-5p inhibitors and siRNA-IRAK2 revealed that negative regulation of miR-424-5p on LPS-induced inflammatory response in BEECs was mediated by IRAK2.Mutually, miR‐424-5p pharmacologic stabilization represents an entirely unique medical aid for cow endometritis and other inflammation‐related diseases.