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Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions

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タイトル: Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions
著者: Ichii, Osamu 著作を一覧する
Otsuka, Saori 著作を一覧する
Sasaki, Nobuya 著作を一覧する
Yabuki, Akira 著作を一覧する
Ohta, Hiroshi 著作を一覧する
Takiguchi, Mitsuyoshi 著作を一覧する
Hashimoto, Yoshiharu 著作を一覧する
Endoh, Daiji 著作を一覧する
Kon, Yasuhiro 著作を一覧する
キーワード: biomarker
chronic kidney disease
collecting duct
distal convoluted tubule
interleukin-1 family member-6
luminal epithelial deciduation
PCR array
tubulointerstitial lesion
発行日: 2010年 3月
出版者: Nature Publishing Group
誌名: Laboratory Investigation
巻: 90
号: 3
開始ページ: 459
終了ページ: 475
出版社 DOI: 10.1038/labinvest.2009.148
抄録: Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In polymerase chain reaction (PCR) array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6.MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the distal convoluted tubules to cortical collecting ducts, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of tubulointerstitial lesions in the B6.MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, transforming growth factor-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with tubulointerstitial lesions and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of tubulointerstitial lesions.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 市居 修


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