Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum

J. Witowski, K. Ksia̧zek, C. Warnecke, M. Kuźlan, K. Korybalska, H. Tayama, J. Wiśniewska-Elnur, K. Pawlaczyk, J. Trómińska, A. Brȩborowicz, A. Jörres

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Recent studies suggest that peritoneal CD4+ T lymphocytes may control recruitment of polymorphonuclear leukocytes (PMN) during peritonitis by an interleukin-17 (IL-17)-dependent mechanism. IL-17 and granulocyte colony-stimulating factor (G-CSF) have been proposed to form an axis that regulates PMN transmigration. Here we report on the role of G-CSF released by human peritoneal mesothelial cells (HPMCs) in IL-17A-mediated peritoneal PMN accumulation. In vitro exposure of HPMCs to IL-17A resulted in a time- and dose-dependent release of G-CSF. This effect was related to the induction of G-CSF mRNA and mediated through the nuclear factor-κB (NF-κB) pathway. The novel observation was that IL-17A-stimulated NF-κB activation in HPMCs followed a biphasic profile, with an early induction (45 min), followed by the return to basal levels (90 min), and a delayed induction (3 h). Tumor necrosis factor α synergistically amplified IL-17A-induced G-CSF production by enhanced NF-κB activation and through stabilization of G-CSF mRNA. Intraperitoneal (i.p.) administration of IL-17A in Balb/c mice resulted in increased local levels of G-CSF and selective PMN accumulation. Administration of anti-G-CSF blocking antibody before IL-17A injection significantly reduced the IL-17A-triggered PMN infiltration. This effect occurred despite increased i.p. levels of PMN-specific chemokines KC and macrophage inflammatory protein-2 seen in animals treated with anti-G-CSF antibody. These data demonstrate that the mesothelium-derived G-CSF plays an important role in IL-17A-induced PMN recruitment into the peritoneum.

Original languageEnglish (US)
Pages (from-to)514-525
Number of pages12
JournalKidney international
Volume71
Issue number6
DOIs
StatePublished - Mar 13 2007

Keywords

  • Chemokines
  • G-CSF
  • IL-17
  • Mesothelium
  • Neutrophils
  • Peritoneum

ASJC Scopus subject areas

  • Nephrology

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    Witowski, J., Ksia̧zek, K., Warnecke, C., Kuźlan, M., Korybalska, K., Tayama, H., Wiśniewska-Elnur, J., Pawlaczyk, K., Trómińska, J., Brȩborowicz, A., & Jörres, A. (2007). Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum. Kidney international, 71(6), 514-525. https://doi.org/10.1038/sj.ki.5002082