RRC ID 67973
Author Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K, Nagai Y, Takeuchi O, Akira S, Matsuguchi T.
Title Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells.
Journal J Immunol
Abstract 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.
Volume 169(4)
Pages 2026-33
Published 2002-8-15
DOI 10.4049/jimmunol.169.4.2026
PMID 12165529
MeSH 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 RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Cell Surface / deficiency Receptors, Cell Surface / genetics Receptors, Cell Surface / immunology* Toll-Like Receptor 1 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptor 5 Toll-Like Receptors p38 Mitogen-Activated Protein Kinases
IF 4.886
Human and Animal Cells RAW 264(RCB0535)