Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Chemokine CXCL1
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Chemokines, CXC / metabolism*
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Chemotactic Factors / biosynthesis
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Chemotactic Factors / genetics
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Chemotactic Factors / immunology
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Chemotactic Factors / metabolism*
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Cycloheximide / pharmacology
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Dactinomycin / pharmacology
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Epithelium / immunology
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Epithelium / metabolism
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Growth Substances / biosynthesis
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Growth Substances / genetics
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Growth Substances / immunology
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Growth Substances / metabolism*
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Humans
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Immune Sera / administration & dosage
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Injections, Intraperitoneal
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Intercellular Signaling Peptides and Proteins*
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Interleukin-17 / administration & dosage
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / immunology
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Interleukin-17 / physiology*
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Male
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Mice
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Mice, Inbred BALB C
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Neutrophil Infiltration / immunology*
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Peritoneum / cytology*
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Peritoneum / immunology*
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Peritoneum / metabolism
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / immunology
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RNA, Messenger / metabolism
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin-17
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Recombinant Proteins / biosynthesis
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Transcription, Genetic / drug effects
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Transcription, Genetic / immunology
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Tumor Necrosis Factor-alpha / physiology
Substances
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CXCL1 protein, human
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Chemokine CXCL1
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Chemokines, CXC
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Chemotactic Factors
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Cxcl1 protein, mouse
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Growth Substances
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IL17RA protein, human
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Il17ra protein, mouse
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Immune Sera
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Intercellular Signaling Peptides and Proteins
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Interleukin-17
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-17
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Dactinomycin
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Cycloheximide