title: Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis.
abstract: OBJECTIVE
  We previously reported that the Val58Ile polymorphism of the leukocyte cell-derived chemotaxin 2 gene (LECT2) is associated with the severity of rheumatoid arthritis (RA). To define the role of LECT2 in inflammatory arthritides, we investigated the development of collagen antibody-induced arthritis (CAIA) in LECT2-deficient (LECT2(-/-)) mice.
  
  
  METHODS
  CAIA was induced in mice by administering anti-type II collagen antibodies followed by lipopolysaccharide. Daily assessment of hind paw swelling was used to monitor the development of arthritis. The histopathologic features and expression of inflammatory cytokines were also analyzed. We confirmed the role of LECT2 by introducing a LECT2 expression vector into LECT2(-/-) mice, using a hydrodynamic gene transfer method.
  
  
  RESULTS
  Arthritis in LECT2(-/-) mice was significantly exacerbated compared with that in wild-type (WT) controls. Histopathologic assessment of the tarsal joints showed that inflammation and erosion of cartilage and bone in LECT2(-/-) mice were more severe than that in controls. Interleukin-1beta (IL-1beta), IL-6, and certain chemokines were present at significantly higher levels in the arthritic hind paws of LECT2(-/-) mice. In contrast, the amount of LECT2 in the serum and locally in the hind paws was higher in arthritic WT mice. Finally, hydrodynamic gene transfer experiments revealed that the severity of arthritis was reduced by the systemic expression of exogenous mouse LECT2 protein in LECT2(-/-) mice.
  
  
  CONCLUSIONS
  These results strongly suggest that LECT2 directly suppresses the development of CAIA. Manipulation of LECT2 might provide a rationale for novel therapeutic approaches to the treatment of inflammatory arthritides such as RA.
authors.affiliation: National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Okumura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Isao
authors.initials: I
authors.lastname: Otani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kojima
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamada
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishida-Okawara
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Nakazato
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Kiichi
authors.initials: K
authors.lastname: Kanayama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000494:pharmacology; D054405:Chemokine CCL3 / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011110:Polymorphism, Genetic; D013640:Tarsal Joints / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001323:Autoantibodies; D054405:Chemokine CCL3; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; C491213:Lect2 protein, mouse; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha