title: Involvement of IL-17 in Fas ligand-induced inflammation.
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.
authors.affiliation: Center for the Development of Molecular Target Drugs, Cancer Research Institute, Graduate School of Medicine Science, Kanazawa University, Takaramachi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.forename: Takaya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Koyo
authors.initials: K
authors.lastname: Shudo
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukui
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Ryu
authors.initials: R
authors.lastname: Imamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor / Q000637:transplantation; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D020381:Interleukin-17; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D008562:Membrane Glycoproteins