Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells

被引:206
作者
Tsuboi, N
Yoshikai, Y
Matsuo, S
Kikuchi, T
Iwami, KI
Nagai, Y
Takeuchi, O
Akira, S
Matsuguchi, T
机构
[1] Nagoya Univ, Sch Med, Res Inst Dis Mechanism & Control, Lab Host Def & Germfree Life,Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Sch Med, Dept Internal Med, Div Nephrol, Nagoya, Aichi 4668550, Japan
[3] Toyama Inst Hlth, Toyama, Japan
[4] Osaka Univ, Dept Host Def, Res Inst Microbial Dis, Osaka, Japan
关键词
D O I
10.4049/jimmunol.169.4.2026
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pyelonephritis, in which renal tubular epithelial cells are directly exposed to bacterial component, is a major predisposing cause of renal insufficiency. Although previous studies have suggested C-C chemokines are involved in the pathogenesis, the exact source and mechanisms of the chemokine secretion remain ambiguous. In this study, we evaluated the involvement of Toll-like receptors (TLRs) in C-C chemokine production by mouse primary renal tubular epithelial cells (MTECs). MTECs constitutively expressed mRNA for TLR1, 2,3,4, and 6, but not for TLR5 or 9. MTECs also expressed MD-2, CD14, myeloid differentiation factor 88, and Toll receptor-IL-1R domain-containing adapter protein/myeloid differentiation factor 88-adapter-like. Synthetic lipid A and lipoprotein induced monocyte chemoattractant protein 1 (MCP-1) and RANTES production in MTECs, which strictly depend on TLR4 and TLR2, respectively. In contrast, MTECs were refractory to CpG-oligodeoxynucleotide in chemokine production, consistently with the absence of TLR9. LPS-mediated MCP-1 and RANTES production in MTECs was abolished by NF-kappaB inhibition, but unaffected by extracellular signal-regulated kinase inhibition. In LPS-stimulated MTECs, inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase significantly decreased RANTES, but did not affect MCP-1 mRNA induction. Thus, MTECs have a distinct expression pattern of TLR and secrete C-C chemokines in response to direct stimulation with a set of bacterial components.
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页码:2026 / 2033
页数:8
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