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 language | English (US) |
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Pages (from-to) | 514-525 |
Number of pages | 12 |
Journal | Kidney international |
Volume | 71 |
Issue number | 6 |
DOIs | |
State | Published - Mar 13 2007 |
Externally published | Yes |
Keywords
- Chemokines
- G-CSF
- IL-17
- Mesothelium
- Neutrophils
- Peritoneum
ASJC Scopus subject areas
- Nephrology