title: Gallium nitrate ameliorates type II collagen-induced arthritis in mice.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Jae-Hyeog
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Kug-Hwan
authors.initials: KH
authors.lastname: Roh
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.affiliation: Shin Tong Pain Clinic, Busan, Republic of Korea.
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Lim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Myoung-Hun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Kwang-rae
authors.initials: KR
authors.lastname: Cho
authors.affiliation: Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea. Electronic address: aneskyj@inje.ac.kr.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D024043:Collagen Type II; D005528:Foot / Q000473:pathology; D005708:Gallium / Q000494:pharmacology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D007074:Immunoglobulin G; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005708:Gallium; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C027235:gallium nitrate
keywords: Collagen type II-induced arthritis; Gallium nitrate; IgG; Matrix metalloproteinases; Nuclear factor κB; Pro-inflammatory cytokines