Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells

Jong Hwan Park, Yungi Kim, Michael Shaw, Thirumala Devi Kanneganti, Yukari Fujimoto, Koichi Fukase, Naohiro Inohara, Gabriel Núñez

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Mesothelial cells that line the serous cavities and outer surface of internal organs are involved in inflammatory responses induced by microbial stimuli and bacterial infection. Upon exposure to bacterial products, mesothelial cells secrete chemokines, but the signaling pathways by which these cells recognize bacteria to mediate innate immune responses remain largely unknown. We report that stimulation of primary peritoneal mesothelial cells via nucleotide-binding oligomerization domain (Nod)1, a member of the intracytoplasmic Nod-like receptor family, induced potent secretion of the chemokines CXCL1 and CCL2 as well as expression of inducible NO synthase and such responses required the kinase RICK. Mesothelial cells also produced chemokines in response to TLR2, TLR3, TLR4, and TLR5 agonists, but unlike that induced by Nod1 stimulation, the TLR-mediated responses were independent of RICK. Yet, Nod1 stimulation of mesothelial cells via RICK enhanced chemokine secretion induced by LPS or IFN-γ and cooperated with IFN-γ in the production of NO. The i.p. administration of KF1B, a synthetic Nod1 agonist, elicited chemokine production in the serum and peritoneal fluid as well as the recruitment of neutrophils into the peritoneal cavity of wild-type mice, but not RICK-deficient mice. Finally, infection of mesothelial cells with Listeria monocytogenes induced production of CXCL1 and this response was significantly reduced in Nod1- or RICK-deficient cells. These results define mesothelial cells as microbial sensors through TLRs and Nod-like receptors and identify Nod1 and RICK as important mediators of chemokine and antimicrobial responses in mesothelial cells.

Original languageEnglish
Pages (from-to)514-521
Number of pages8
JournalJournal of Immunology
Volume179
Issue number1
Publication statusPublished - 2007 Jul 1
Externally publishedYes

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Chemokines
Innate Immunity
Nucleotides
Chemokine CXCL1
Neutrophil Infiltration
Chemokine CCL2
Ascitic Fluid
Peritoneal Cavity
Listeria monocytogenes
Bacterial Infections
Nitric Oxide Synthase
Phosphotransferases
Bacteria
Cell Line
Infection
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. / Park, Jong Hwan; Kim, Yungi; Shaw, Michael; Kanneganti, Thirumala Devi; Fujimoto, Yukari; Fukase, Koichi; Inohara, Naohiro; Núñez, Gabriel.

In: Journal of Immunology, Vol. 179, No. 1, 01.07.2007, p. 514-521.

Research output: Contribution to journalArticle

Park, JH, Kim, Y, Shaw, M, Kanneganti, TD, Fujimoto, Y, Fukase, K, Inohara, N & Núñez, G 2007, 'Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells', Journal of Immunology, vol. 179, no. 1, pp. 514-521.
Park, Jong Hwan ; Kim, Yungi ; Shaw, Michael ; Kanneganti, Thirumala Devi ; Fujimoto, Yukari ; Fukase, Koichi ; Inohara, Naohiro ; Núñez, Gabriel. / Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. In: Journal of Immunology. 2007 ; Vol. 179, No. 1. pp. 514-521.
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