PMID- 37175545 OWN - NLM STAT- MEDLINE DCOM- 20230515 LR - 20230515 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 9 DP - 2023 Apr 25 TI - Myd88 Signaling Is Involved in the Inflammatory Response in LPS-Induced Mouse Epididymitis and Bone-Marrow-Derived Dendritic Cells. LID - 10.3390/ijms24097838 [doi] LID - 7838 AB - Epididymitis is an epididymal inflammation that may lead to male infertility. Dendritic cells (DCs) and myeloid differentiation primary response gene 88 (Myd88) were associated with epididymitis in rodents. However, the functions of Myd88 on epididymal DCs remain unclear. This study investigated the role of Myd88 in DCs for epididymitis. The Myd88 signaling pathway, phenotypes of DC subsets, and cytokines were investigated in lipopolysaccharide (LPS)-induced epididymitis in mice. CRISPR-Cas9 was used to knockout Myd88 in bone-marrow-derived dendritic cells (BMDCs) and immortalized mouse epididymal (DC2) cell line. In the vivo experiments, levels of the proinflammatory cytokines IL-1alpha, IL-6, IL-17A, TNF-alpha, IL-1beta, MCP-1, and GM-CSF, mRNA for MyD88 related genes, and the percentages of monocyte-derived DCs (Mo-DCs) were significantly elevated in mice with epididymitis. In the vitro experiments, LPS significantly promoted the apoptosis of BMDCs. In addition, the concentration of inflammatory cytokines in BMDCs and DC2s were increased in the LPS group, while decreasing after the knockout of Myd88. These findings indicate that Myd88 on DCs is involved in the inflammation of epididymitis in mice, which may be a potential target for better strategies regarding the treatment of immunological male infertility. FAU - Liu, Jin-Chuan AU - Liu JC AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. AD - Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Wang, Peng AU - Wang P AD - Department of Urology, Daping Hospital, Army Medical University, Chongqing 400042, China. FAU - Zeng, Qun-Xiong AU - Zeng QX AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. AD - Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Yang, Chen AU - Yang C AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. FAU - Lyu, Minmin AU - Lyu M AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. FAU - Li, Yanfeng AU - Li Y AD - Department of Urology, Daping Hospital, Army Medical University, Chongqing 400042, China. FAU - Yeung, William Shu-Biu AU - Yeung WS AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. AD - Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Chiu, Philip Chi-Ngong AU - Chiu PC AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. AD - Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Haidl, Gerhard AU - Haidl G AD - Department of Andrology, Bonn University Hospital, Campus-Venusberg 1, 53127 Bonn, Germany. FAU - Allam, Jean-Pierre AU - Allam JP AD - Department of Andrology, Bonn University Hospital, Campus-Venusberg 1, 53127 Bonn, Germany. FAU - Duan, Yong-Gang AU - Duan YG AUID- ORCID: 0000-0002-5350-892X AD - Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China. LA - eng GR - JCYJ20180306173803232/Shenzhen Fundamental Research Program/ GR - cstc2020jcyj-msxmX0186/Natural Science Foundation of Chongqing, China/ GR - GJHZ20200731095006018/Science, Technology, and Innovation Commission of Shenzhen/ PT - Journal Article DEP - 20230425 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Lipopolysaccharides) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Cytokines) RN - 0 (Myd88 protein, mouse) SB - IM MH - Humans MH - Male MH - Animals MH - Mice MH - *Epididymitis/metabolism MH - Lipopolysaccharides/pharmacology MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - Bone Marrow/metabolism MH - Dendritic Cells MH - Signal Transduction MH - Cytokines/metabolism MH - Inflammation/metabolism MH - Mice, Inbred C57BL PMC - PMC10178089 OTO - NOTNLM OT - CRISPR-Cas9 OT - Myd88 OT - dendritic cells OT - epididymitis OT - male infertility COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2023/05/13 15:13 MHDA- 2023/05/15 11:42 PMCR- 2023/04/25 CRDT- 2023/05/13 01:27 PHST- 2023/03/06 00:00 [received] PHST- 2023/03/30 00:00 [revised] PHST- 2023/04/20 00:00 [accepted] PHST- 2023/05/15 11:42 [medline] PHST- 2023/05/13 15:13 [pubmed] PHST- 2023/05/13 01:27 [entrez] PHST- 2023/04/25 00:00 [pmc-release] AID - ijms24097838 [pii] AID - ijms-24-07838 [pii] AID - 10.3390/ijms24097838 [doi] PST - epublish SO - Int J Mol Sci. 2023 Apr 25;24(9):7838. doi: 10.3390/ijms24097838.