RRC ID 28680
Author Umemura M, Kawabe T, Shudo K, Kidoya H, Fukui M, Asano M, Iwakura Y, Matsuzaki G, Imamura R, Suda T.
Title Involvement of IL-17 in Fas ligand-induced inflammation.
Journal Int Immunol
Abstract Fas ligand (FasL) has been well characterized as a death factor. However, recent studies revealed that ectopic expression of FasL induces inflammation associated with massive neutrophil infiltration. We previously demonstrated that the neutrophil infiltration-inducing activity of FasL is partly dependent on, but partly independent of, IL-1beta. Here we investigated the cytokine profile of peritoneal lavage fluid obtained from mice that received i.p. injections of FFL, a FasL-expressing tumor cell line. We found that FFL injection caused a marked increase of not only IL-1beta but also IL-6, IL-17, IL-18, KC/chemokine CXC ligand 1 and macrophage inflammatory protein (MIP)-2, but not of IL-1alpha, IFN-gamma, TGF-beta or TNF-alpha. The FFL-induced cytokine production was not observed in Fas-deficient lpr mice. Among cells transfected to express individually IL-1beta, IL-6, IL-17, or IL-18, only those expressing IL-1beta and IL-17 induced neutrophil infiltration. In these analyses, as little as 20 pg of peritoneal IL-17 induced neutrophil infiltration. The peritoneal IL-17 levels after FFL-injection were greatly diminished in IL-1-deficient mice. However, the IL-17 level was still above the threshold for neutrophil infiltration. Consistent with this, co-administration of the anti-IL-17 antibody with FFL diminished the peritoneal KC levels and neutrophil infiltration in IL-1-deficient mice. In addition, the expression of IL-17 by the tumor cells inhibited tumor growth in wild-type and nude mice. These results indicate that FasL is an upstream inflammatory factor that induces a variety of other inflammatory cytokines in vivo, and suggest that IL-17 is involved in FasL-induced inflammation in the absence of IL-1beta.
Volume 16(8)
Pages 1099-108
Published 2004-8-1
DOI 10.1093/intimm/dxh111
PII dxh111
PMID 15237105
MeSH Animals Antibodies, Monoclonal / administration & dosage Antibodies, Monoclonal / immunology* Antigens, Differentiation, T-Lymphocyte / administration & dosage Antigens, Differentiation, T-Lymphocyte / immunology* Cell Line, Tumor / transplantation Cell Movement / drug effects Cell Movement / immunology Cytokines / immunology Fas Ligand Protein Gene Expression Regulation / drug effects Gene Expression Regulation / immunology Inflammation / chemically induced Inflammation / immunology Interleukin-17 Membrane Glycoproteins / genetics Membrane Glycoproteins / immunology* Mice Mice, Knockout Neutrophils / immunology*
IF 3.519
Times Cited 46
DNA material pMOS-mIL6 (RDB07953) pEF-mIL6 (RDB07954) pMOS-mIL17 (RDB07955) pEF-mIL17 (RDB07956)