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Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice

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Title: Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice
Authors: Masum, M. A. Browse this author
Ichii, O. Browse this author →KAKEN DB
ELewa, Y. H. A. Browse this author
Kon, Y. Browse this author →KAKEN DB
Keywords: Toll-like receptor 9
peritubular capillary
tubulointerstitial lesions
autoimmune glomerulonephritis
BXSB
MpJ-Yaa mice
Issue Date: Mar-2019
Publisher: SAGE Publications
Journal Title: Lupus
Volume: 28
Issue: 3
Start Page: 324
End Page: 333
Publisher DOI: 10.1177/0961203319828518
Abstract: Background Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. Methods Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. Results Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta (Il1b), Il6, interferon gamma (Ifng), and tumor necrosis factor alpha (Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules (P<0.05 and 0.01). Conclusion Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.
Rights: M.A. Masum, O. Ichii, Y.H.A. ELewa, and Y. Kon, Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice, Lupus 28(3) pp. 324-333. Copyright © 2019 M.A. Masum, O. Ichii, Y.H.A. ELewa, and Y. Kon. DOI: 10.1177/0961203319828518.
Type: article (author version)
URI: http://hdl.handle.net/2115/75181
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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