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

Ichii, Osamu; Otsuka, Saori; Sasaki, Nobuya; Yabuki, Akira; Ohta, Hiroshi; Takiguchi, Mitsuyoshi; Hashimoto, Yoshiharu; Endoh, Daiji; Kon, Yasuhiro

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

Ichii, Osamu; Otsuka, Saori; Sasaki, Nobuya et al.

Laboratory Investigation, 2010, 90(3), 459-475

Permalink : https://hdl.handle.net/2115/43816

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アクセス権	open access
URI	https://hdl.handle.net/2115/43816
タイトル	Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions
著者	Ichii, Osamu ; Otsuka, Saori ; Sasaki, Nobuya ; Yabuki, Akira ; Ohta, Hiroshi ; Takiguchi, Mitsuyoshi ; Hashimoto, Yoshiharu ; Endoh, Daiji ; Kon, Yasuhiro
e-Rad_Researcher 60547769 著者名 Ichii, Osamu
e-Rad_Researcher 10566152 著者名 Otsuka, Saori
e-Rad_Researcher 20302614 著者名 Sasaki, Nobuya
e-Rad_Researcher 10315400 著者名 Yabuki, Akira
e-Rad_Researcher 50431333 著者名 Ohta, Hiroshi
e-Rad_Researcher 70261336 著者名 Takiguchi, Mitsuyoshi
e-Rad_Researcher 20091481 著者名 Hashimoto, Yoshiharu
著者名 Endoh, Daiji
e-Rad_Researcher 10178402 著者名 Kon, Yasuhiro
言語	英語
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	2010-03
出版者	Nature Publishing Group
収録物名	Laboratory Investigation
巻(号)	90(3)
ページ	459-475
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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0023-6837
関連情報	PMID 20101239
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/labinvest.2009.148