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Exacerbation of Collagen Antibody–Induced Arthritis in Transgenic Mice Overexpressing Peroxiredoxin 6
Author(s) -
Kim Dae Hwan,
Lee Dong Hun,
Jo Mi Ran,
Son Dong Ju,
Park Mi Hee,
Hwang Chul Ju,
Park Ju Ho,
Yuk Dong Yeon,
Yoon Do Young,
Jung YoungSuk,
Kim Youngsoo,
Jeong Jae Hwang,
Han Sang Bae,
Hong Jin Tae
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39284
Subject(s) - peroxiredoxin , proinflammatory cytokine , arthritis , genetically modified mouse , transgene , immunology , inflammation , microbiology and biotechnology , transfection , biology , cell culture , biochemistry , enzyme , peroxidase , genetics , gene
Objective Peroxiredoxin 6 plays important and complex roles in the process of inflammation, but its role in the development of rheumatoid arthritis (RA) remains unclear. We undertook this study to investigate the roles and mechanisms of peroxiredoxin 6 in the development of collagen antibody–induced arthritis (CAIA) and antigen‐induced arthritis (AIA) in peroxiredoxin 6–overexpressing transgenic mice, in peroxiredoxin 6–transfected RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients. Methods CAIA and AIA were induced using standard methods. Peroxiredoxin 6–transfected RAW 264.7 cells, macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and synoviocytes from arthritis patients were used to study proinflammatory responses and mechanisms. Clinical scores and histopathologic changes were determined in peroxiredoxin 6–overexpressing transgenic mice and wild‐type (WT) mice with CAIA or AIA. Generation of nitric oxide (NO), expression of inducible NO synthase and cyclooxygenase 2, and activity of NF‐κB and activator protein 1 (AP‐1) were determined in cultured macrophages and synoviocytes as well as in joint tissue from mice by Western blotting, electrophoretic mobility shift assay, and immunohistochemical analysis. Results Development of CAIA and AIA and proinflammatory responses were more exacerbated in peroxiredoxin 6–overexpressing transgenic mice than in WT mice. Overexpression of peroxiredoxin 6 increased lipopolysaccharide‐induced inflammatory responses in RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients, and this was accompanied by up‐regulation of the JNK pathway. Moreover, a JNK inhibitor completely blocked RA development and proinflammatory responses. Conclusion Our findings suggest that overexpression of peroxiredoxin 6 might promote development of RA through NF‐κB and AP‐1 activity via the JNK pathway.