title: Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: cooperation between growth-related protein and IL-8, and interrelated regulation among TNFalpha, IL-1, IL-1 receptor antagonist, IL-8, and growth-related protein.
abstract: We investigated the functional role of a CXC chemokine, growth-related protein (GRO), in the recruitment of neutrophils in lipopolysaccharide (LPS)-induced rabbit arthritis. The amounts of GRO in the synovial fluids (SF) reached the first peak (major) at 2 hours and the second peak (minor) at 9 hours after injection of LPS into the knee joints. Administration of anti-GRO mouse monoclonal antibody inhibited 54% of the peak leukocyte accumulation at 9 hours (neutrophils greater than 95%), which was similar to the inhibition by anti-IL-8 IgG (48%). Co-administration of these inhibitors increased the inhibition up to 70% at 9 hours and also inhibited 65% of the initial phase of leukocyte infiltration at 2 hours (neutrophils greater than 99%), which was not affected by a single administration of each inhibitor. The amounts of GRO in SF at 2 hours were not altered by either anti-TNFalpha mAb or anti-IL-8 IgG, but reduced by rabbit recombinant IL-1 receptor antagonist (rrlL-1Ra) by 39%. The inhibition by rrlL-1 Ra was augmented further to 59% with coadministered anti-TNFalpha mAb. In contrast, the amounts of GRO at 9 hours were reduced by rrlL-1Ra by 67%. There was no additional reduction in the amounts of GRO at 9 hours by either combination of rrlL-1Ra with anti-TNFalpha mAb or anti-IL-8 IgG. Administration of anti-GRO mAb did not alter TNFalpha or IL-8 contents in SF at their peak (2 hours), but reduced the amounts of IL-1beta at 6 hours and IL-1Ra at 9 hours by 42% and 49%, respectively. These results provide evidence for the following: (a) GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils both in the early and the late phase of LPS-induced arthritis, (b) IL-1 produced in the early phase stimulates GRO production, (c) GRO plays a role in the later induction of IL-1beta and IL-1Ra, and (d) induction of GRO is not regulated by IL-8.
authors.affiliation: Department of Pathology, Kumamoto University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsukawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Ohkawara
authors.forename: M
authors.initials: M
authors.lastname: Yoshinaga
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D002460:Cell Line; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015200:Fluoroimmunoassay; D006133:Growth Substances / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012795:Sialoglycoproteins / Q000276:immunology / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019743:Chemokines, CXC; D006133:Growth Substances; C507764:Il1rn protein, mouse; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha