Roles of Toll-Like Receptors in C-C Chemokine Production by Renal Tubular Epithelial Cells

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 secret...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-08, Vol.169 (4), p.2026-2033
Main Authors: Tsuboi, Naotake, Yoshikai, Yasunobu, Matsuo, Seiichi, Kikuchi, Takeshi, Iwami, Ken-Ichiro, Nagai, Yoshiyuki, Takeuchi, Osamu, Akira, Shizuo, Matsuguchi, Tetsuya
Format: Article
Language:English
Subjects:
Animals
Cell Line
Chemokine CCL2 - biosynthesis
Chemokine CCL2 - genetics
Chemokine CCL5 - biosynthesis
Chemokine CCL5 - genetics
Chemokines, CC - biosynthesis
Chemokines, CC - genetics
Cytokines - pharmacology
Drosophila Proteins
Epithelial Cells - drug effects
Epithelial Cells - immunology
Epithelial Cells - metabolism
Gene Expression
JNK Mitogen-Activated Protein Kinases
Kidney Tubules - cytology
Kidney Tubules - drug effects
Kidney Tubules - immunology
Kidney Tubules - metabolism
Lipid A - pharmacology
Lipopolysaccharides - pharmacology
Membrane Glycoproteins - deficiency
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinases - metabolism
Oligodeoxyribonucleotides - pharmacology
p38 Mitogen-Activated Protein Kinases
Receptors, Cell Surface - deficiency
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Toll-Like Receptor 1
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 5
Toll-Like Receptors
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.169.4.2026