Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions.
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 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 DCTs to CCDs, 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 TILs 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, TGF-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 TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
Ichii
Osamu
O
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Otsuka
Saori
S
Sasaki
Nobuya
N
Yabuki
Akira
A
Ohta
Hiroshi
H
Takiguchi
Mitsuyoshi
M
Hashimoto
Yoshiharu
Y
Endoh
Daiji
D
Kon
Yasuhiro
Y
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; C543716:interleukin 1F6, mouse