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

Naotake Tsuboi, Yasunobu Yoshikai, Seiichi Matsuo, Takeshi Kikuchi, Ken Ichiro Iwami, Yoshiyuki Nagai, Osamu Takeuchi, Shizuo Akira, Tetsuya Matsuguchi

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    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-κB 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.

    Original languageEnglish
    Pages (from-to)2026-2033
    Number of pages8
    JournalJournal of Immunology
    Volume169
    Issue number4
    DOIs
    Publication statusPublished - Aug 15 2002

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    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Tsuboi, N., Yoshikai, Y., Matsuo, S., Kikuchi, T., Iwami, K. I., Nagai, Y., ... Matsuguchi, T. (2002). Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. Journal of Immunology, 169(4), 2026-2033. https://doi.org/10.4049/jimmunol.169.4.2026