Inhibition of CXCR4 by MicroRNA-1192 Reduces the Activation of Th17 Cells and Expression of Inflammation Factors in a Mouse Model of Vulvovaginal Candidiasis

• Published in: Cellular physiology and biochemistry Vol. 50; no. 3; pp. 893 - 910
• Main Authors: Liu, Jing, Wang, Huai-Zhen, Sun, Yong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: 3' Untranslated Regions; Alcohol; Animals; Antagomirs - metabolism; Apoptosis; Binding sites; Breast cancer; Candidiasis, Vulvovaginal - immunology; Candidiasis, Vulvovaginal - microbiology; Candidiasis, Vulvovaginal - pathology; Cell adhesion & migration; Cell Cycle Checkpoints; Cell growth; Chemokines; Colorectal cancer; CXCR4; Disease Models, Animal; Ethics; Experiments; Female; Gene expression; Infections; Inflammation factors; Interleukin-17 - analysis; Interleukin-17 - chemistry; Interleukin-17 - metabolism; Interleukin-23 - analysis; Interleukin-23 - genetics; Interleukin-23 - metabolism; Interleukin-6 - analysis; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kinases; Mice; Mice, Inbred BALB C; MicroRNA-1192; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Retracted Paper; RNA Interference; RNA, Small Interfering - metabolism; Th17 cell; Th17 Cells - cytology; Th17 Cells - metabolism; Vulvovaginal candidiasis; Womens health; Beijing China; China; Vulvovaginal candidiasis; CXCR4; Inflammation factors; Th17 cell; MicroRNA-1192
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000494475

Background/Aims: Vulvovaginal candidiasis (VVC) is a disease commonly occurring in sexually active women. The involvement of microRNAs in several kinds of infectious diseases has been highlighted in a number of researches. Therefore, we conducted the present study in order to investigate whether microRNA-1192 (miR-1192) would significantly target CXCR4 in Th17 cells as well as inflammatory factors in mouse models suffering from VVC. Methods: Seventy-five mice were selected as test subjects for this study, of which twenty-five were used as the normal control, while the rest were treated with estradiol or oil-treated in order to establish VVC mouse models (each n = 25). Protein expressions of CXCR4, IL-6, IL-17, and IL-23 were all measured using both an immunohistochemistry and ELISA. The Th17 cell percentage in peripheral blood and the expression of RORγt in Th17 cells were detected using a flow cytometry. Mouse vaginal epithelial cells were isolated from normal mice, after which the mice were treated with estradiol to regulate their estrogen, followed by treatments involving the miR-1192 mimic, miR-1192 inhibitor, siRNA-CXCR4, and miR-1192 inhibitor + si-CXCR4. The cell cycle, apoptosis, and proliferation were all examined by using an additional flow cytometry as well as the employment of the MTT assay. The miR-1192, CXCR4, IL-6, IL-17, and IL-23 expressions in tissues and cells were both measured using both RT-qPCR and western blot assay techniques. Results: The mice treated with either estradiol or oil had presented to us lowered levels in miR-1192 expression as well as higher levels in both Th17 cell percentage and expression of RORγt in Th17 cells, along with mRNA and protein expressions of CXCR4, IL-6, IL-17, and IL-23. In cell experiments, the mouse vaginal epithelial cells that had been treated with miR-1192 inhibitor had shown us a decreased cell proliferation rate and contrarily increased expressions of CXCR4, IL-6, IL-17, and IL-23 mRNA, protein, and cell apoptosis rate; these results were opposite to the ones found in the mice treated with miR-1192 mimic. Conclusion: Our results provided significant evidence that miR-1192 could directly development and progression of VVC by restraining the CXCR4 gene in the VVC mice.