IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells.
IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GROalpha). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROalpha mRNA and protein. Combination of IL-17 together with TNF-alpha resulted in an increased stability of GROalpha mRNA and synergistic release of GROalpha protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.
Witowski
J
J
Department of Pathophysiology, University Medical School, Poznan, Poland.
Pawlaczyk
K
K
Breborowicz
A
A
Scheuren
A
A
Kuzlan-Pawlaczyk
M
M
Wisniewska
J
J
Polubinska
A
A
Friess
H
H
Gahl
G M
GM
Frei
U
U
Jörres
A
A
D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism*; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D010537:Peritoneum / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; C109985:IL17RA protein, human; C491673:Il17ra protein, mouse; D007106:Immune Sera; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide