A critical role for allograft inflammatory factor-1 in the pathogenesis of rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is characterized by massive synovial proliferation, angiogenesis, subintimal infiltration of inflammatory cells and the production of cytokines such as TNF-alpha and IL-6. Allograft inflammatory factor-1 (AIF-1) has been identified in chronic rejection of rat cardiac allografts as well as tissue inflammation in various autoimmune diseases. AIF-1 is thought to play an important role in chronic immune inflammatory processes, especially those involving macrophages. In the current work, we examined the expression of AIF-1 in synovial tissues and measured AIF-1 in synovial fluid (SF) derived from patients with either RA or osteoarthritis (OA). We also examined the proliferation of synovial cells and induction of IL-6 following AIF-1 stimulation. Immunohistochemical staining showed that AIF-1 was strongly expressed in infiltrating mononuclear cells and synovial fibroblasts in RA compared with OA. Western blot analysis and semiquantitative RT-PCR analysis demonstrated that synovial expression of AIF-1 in RA was significantly greater than the expression in OA. AIF-1 induced the proliferation of cultured synovial cells in a dose-dependent manner and increased the IL-6 production of synovial fibroblasts and PBMC. The levels of AIF-1 protein were higher in synovial fluid from patients with RA compared with patients with OA (p < 0.05). Furthermore, the concentration of AIF-1 significantly correlated with the IL-6 concentration (r = 0.618, p < 0.01). These findings suggest that AIF-1 is closely associated with the pathogenesis of RA and is a novel member of the cytokine network involved in the immunological processes underlying RA.

• Authors: Mizuho Kimura, Yutaka Kawahito, Hiroshi Obayashi, Mitsuhiro Ohta, Hirokazu Hara, Tetsuo Adachi, Daisaku Tokunaga, Tatsuya Hojo, Masahide Hamaguchi, Atsushi Omoto, Hidetaka Ishino, Makoto Wada, Masataka Kohno, Yasunori Tsubouchi, Toshikazu Yoshikawa
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 5 Pg. 3316-22 (Mar 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17312183 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• AIF1 protein, human
• Calcium-Binding Proteins
• DNA-Binding Proteins
• Interleukin-6
• Microfilament Proteins

Topics

• Animals
• Arthritis, Rheumatoid (immunology, metabolism, pathology, physiopathology)
• Calcium-Binding Proteins
• DNA-Binding Proteins (biosynthesis, immunology)
• Female
• Fibroblasts (immunology, metabolism, pathology)
• Gene Expression Regulation
• Humans
• Interleukin-6 (immunology, metabolism)
• Male
• Microfilament Proteins
• Middle Aged
• Osteoarthritis (immunology, metabolism, pathology, physiopathology)
• Rats
• Synovial Fluid (immunology, metabolism)