Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum.
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-kappaB (NF-kappaB) pathway. The novel observation was that IL-17A-stimulated NF-kappaB 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 alpha synergistically amplified IL-17A-induced G-CSF production by enhanced NF-kappaB 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.
Witowski
J
J
Department of Pathophysiology, University Medical School, Poznan, Poland.
Ksiazek
K
K
Warnecke
C
C
Kuźlan
M
M
Korybalska
K
K
Tayama
H
H
Wiśniewska-Elnur
J
J
Pawlaczyk
K
K
Trómińska
J
J
Breborowicz
A
A
Jörres
A
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004848:Epithelium; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D010537:Peritoneum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020381:Interleukin-17; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor