PMID- 33827102 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20210624 IS - 1423-0143 (Electronic) IS - 1420-4096 (Linking) VI - 46 IP - 2 DP - 2021 TI - Interleukin-6 via Toll-Like Receptor 3 Signaling Attenuates the Expression of Proinflammatory Chemokines in Human Podocytes. PG - 207-218 LID - 10.1159/000514589 [doi] AB - BACKGROUND: Although toll-like receptor 3 (TLR3) signaling is involved in the development of certain chronic kidney diseases, the specific molecular mechanisms underlying inflammatory reactions via activation of TLR3 signaling in human podocytes remain unclear. Interleukin (IL)-6 is a pleiotropic cytokine associated with innate and adaptive immune responses; however, little is known about the implication of IL-6 via the activation of regional TLR3 signaling in the inflammatory reactions in human podocytes. METHODS: We treated immortalized human podocytes with polyinosinic-polycytidylic acid (poly IC), an authentic viral double-stranded RNA, and assessed the expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5) using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against IFN-beta and IL-6. RESULTS: We found that the activation of TLR3 induced expression of IL-6, MCP-1, CCL5, and IFN-beta in human podocytes. RNA interference experiments revealed that IFN-beta was involved in the poly IC-induced expression of IL-6, MCP-1, and CCL5. Interestingly, IL-6 knockdown markedly increased the poly IC-induced expression of MCP-1 and CCL5. Further, treatment of cells with IL-6 attenuated the expression of CCL5 and MCP-1 mRNA and proteins. CONCLUSION: IL-6 induced by TLR3 signaling negatively regulates the expression of representative TLR3 signaling-dependent proinflammatory chemokines in human podocytes. CI - (c) 2021 The Author(s). Published by S. Karger AG, Basel. FAU - Umetsu, Hidenori AU - Umetsu H AD - Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Watanabe, Shojiro AU - Watanabe S AD - Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Imaizumi, Tadaatsu AU - Imaizumi T AD - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Aizawa, Tomomi AU - Aizawa T AD - Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Tsugawa, Koji AU - Tsugawa K AD - Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Kawaguchi, Shogo AU - Kawaguchi S AD - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Seya, Kazuhiko AU - Seya K AD - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Matsumiya, Tomoh AU - Matsumiya T AD - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. FAU - Tanaka, Hiroshi AU - Tanaka H AD - Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. AD - Department of School Health Science, Hirosaki University Faculty of Education, Hirosaki, Japan. LA - eng PT - Journal Article DEP - 20210407 PL - Switzerland TA - Kidney Blood Press Res JT - Kidney & blood pressure research JID - 9610505 RN - 0 (Chemokines) RN - 0 (Interleukin-6) RN - 0 (Toll-Like Receptor 3) SB - IM MH - Chemokines/*metabolism MH - Humans MH - Inflammation/*metabolism MH - Interleukin-6/*metabolism MH - Podocytes/*metabolism MH - Signal Transduction/*immunology MH - Toll-Like Receptor 3/*metabolism OTO - NOTNLM OT - C-C motif chemokine ligand 5 OT - Interleukin-6 OT - Monocyte chemoattractant protein-1 OT - Podocytes OT - Toll-like receptor 3 EDAT- 2021/04/08 06:00 MHDA- 2021/06/25 06:00 CRDT- 2021/04/07 20:16 PHST- 2020/09/23 00:00 [received] PHST- 2021/01/20 00:00 [accepted] PHST- 2021/04/08 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2021/04/07 20:16 [entrez] AID - 000514589 [pii] AID - 10.1159/000514589 [doi] PST - ppublish SO - Kidney Blood Press Res. 2021;46(2):207-218. doi: 10.1159/000514589. Epub 2021 Apr 7.