title: Lipopolysaccharide accelerates collagen-induced arthritis in association with rapid and continuous production of inflammatory mediators and anti-type II collagen antibody.
abstract: Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis (RA). Lipopolysaccharide (LPS) is known to accelerate CIA; however, the pathogenetic mechanisms are not yet fully understood. In this study, type II collagen (CII)-immunized mice were found to have marked increases in degree of expression of mRNA of inflammatory mediators such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and macrophage inflammatory protein-2 (MIP-2) in their arthritic paws and of serum anti-CII antibody concentration before the onset of arthritis induced by LPS injection. The gene expression was rapid and continuous after direct activation of nuclear factor κB. The amounts of mRNA of TNF-α, IL-1β, and MIP-2, as well as of matrix metalloproteinases and the receptor activator of nuclear factor κB ligand, increased with the development of arthritis, correlated positively with clinical severity and corresponded with histopathological changes. Moreover, anti-TNF-α neutralizing antibody inhibited the development of LPS-accelerated CIA and a single injection of recombinant mouse TNF-α induced increases in anti-CII antibody concentrations, suggesting TNF-α may contribute to the development of arthritis by both initiation of inflammation and production of autoantibodies. These data suggest that exacerbation of RA by LPS is associated with rapid and continuous production of inflammatory mediators and autoantibodies.
authors.affiliation: Frontier Research Laboratories, Daiichi Sankyo Co., Ltd., 1‐2‐58 Hiromachi, Tokyo 140‐8710, Japan. tanaka.shinji.fv@daiichisankyo.co.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Toki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Akimoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Morishita
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D054426:Chemokine CXCL2 / Q000096:biosynthesis* / Q000235:genetics; D024043:Collagen Type II / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001323:Autoantibodies; D054426:Chemokine CXCL2; D024043:Collagen Type II; C404915:Cxcl2 protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha