title: Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis.
abstract: OBJECTIVE
  Galectin 3, an endogenous β-galactoside-binding lectin, plays an important role in the modulation of immune responses. The finding that galectin 3 is present in the inflamed synovium in patients with rheumatoid arthritis suggests that the protein is associated with the pathogenesis of this disease. We undertook this study to investigate the influence of galectin 3 deficiency in a murine model of arthritis.
  
  
  METHODS
  Wild-type (WT) and galectin 3-deficient (galectin 3(-/-) ) mice were subjected to antigen-induced arthritis (AIA) through immunization with methylated bovine serum albumin. The concentration of serum cytokines (interleukin-6 [IL-6] and tumor necrosis factor α [TNFα]) and antigen-specific antibodies was evaluated using a cytometric bead array platform and enzyme-linked immunosorbent assay (ELISA). Cellular IL-17 responses were examined by flow cytometry, ELISA, and enzyme-linked immunospot assay.
  
  
  RESULTS
  The joint inflammation and bone erosion of AIA were markedly suppressed in galectin 3(-/-) mice as compared with WT mice. The reduced arthritis in galectin 3(-/-) mice was accompanied by decreased levels of antigen-specific IgG and proinflammatory cytokines. The frequency of IL-17-producing cells in the spleen was reduced in galectin 3(-/-) mice as compared with WT mice. Exogenously added recombinant galectin 3 could partially restore the reduced arthritis and cytokines in galectin 3(-/-) mice.
  
  
  CONCLUSIONS
  Our findings show that galectin 3 plays a pathogenic role in the development and progression of AIA and that the disease severity is accompanied by alterations of antigen-specific IgG levels, systemic levels of TNFα and IL-6, and frequency of IL-17-producing T cells. To our knowledge, this is the first report of in vivo evidence that galectin 3 plays a crucial role in the development of arthritis.
authors.affiliation: University of Gothenburg, Gothenburg, Sweden. Huamei.Forsman@rheuma.gu.se
authors.forename: Huamei
authors.initials: H
authors.lastname: Forsman
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.forename: Emil
authors.initials: E
authors.lastname: Andréasson
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.forename: Karin
authors.initials: K
authors.lastname: Onnheim
authors.forename: Alexandra
authors.initials: A
authors.lastname: Karlström
authors.forename: Karin
authors.initials: K
authors.lastname: Sävman
authors.forename: Mattias
authors.initials: M
authors.lastname: Magnusson
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Brown
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3 / Q000378:metabolism* / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology*; D012709:Serum Albumin / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013264:Stifle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D037502:Galectin 3; D020381:Interleukin-17; D015850:Interleukin-6; D011994:Recombinant Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha