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

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Title: Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions
Authors: Ichii, Osamu Browse this author →KAKEN DB
Otsuka, Saori Browse this author →KAKEN DB
Sasaki, Nobuya Browse this author →KAKEN DB
Yabuki, Akira Browse this author →KAKEN DB
Ohta, Hiroshi Browse this author →KAKEN DB
Takiguchi, Mitsuyoshi Browse this author →KAKEN DB
Hashimoto, Yoshiharu Browse this author →KAKEN DB
Endoh, Daiji Browse this author
Kon, Yasuhiro Browse this author →KAKEN DB
Keywords: biomarker
chronic kidney disease
collecting duct
distal convoluted tubule
interleukin-1 family member-6
luminal epithelial deciduation
PCR array
tubulointerstitial lesion
Issue Date: Mar-2010
Publisher: Nature Publishing Group
Journal Title: Laboratory Investigation
Volume: 90
Issue: 3
Start Page: 459
End Page: 475
Publisher DOI: 10.1038/labinvest.2009.148
PMID: 20101239
Abstract: 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.
Type: article (author version)
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)

Submitter: 市居 修

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