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IL-36 alpha Regulates Tubulointerstitial Inflammation in the Mouse Kidney
This item is licensed under:Creative Commons Attribution 4.0 International
Title: | IL-36 alpha Regulates Tubulointerstitial Inflammation in the Mouse Kidney |
Authors: | Ichii, Osamu Browse this author →KAKEN DB | Kimura, Junpei Browse this author | Okamura, Tadashi Browse this author | Horino, Taro Browse this author | Nakamura, Teppei Browse this author | Sasaki, Hayato Browse this author | Elewa, Yaser Hosny Ali Browse this author →ORCID | Kon, Yasuhiro Browse this author →KAKEN DB |
Keywords: | inflammation | distal tubule | IL-36 alpha | tubulointerstitial lesion | unilateral ureter obstruction | folic acid |
Issue Date: | 23-Oct-2017 |
Publisher: | Frontiers Media |
Journal Title: | Frontiers in immunology |
Volume: | 8 |
Start Page: | 1346 |
Publisher DOI: | 10.3389/fimmu.2017.01346 |
Abstract: | IL-36 alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36 alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36 alpha in kidney injury. IL-36 alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36 alpha localized to dilated DTs. IL-36 alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36 alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36 alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36 alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36 alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36 alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36 alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36 alpha may be a novel kidney injury marker useful for evaluating DT damages. |
Rights: | © 2017 Ichii, Kimura, Okamura, Horino, Nakamura, Sasaki, Elewa and Kon | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/70804 |
Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 市居 修
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