title: Exacerbation of collagen antibody-induced arthritis in transgenic mice overexpressing peroxiredoxin 6.
abstract: 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.
  
  
  CONCLUSIONS
  Our findings suggest that overexpression of peroxiredoxin 6 might promote development of RA through NF-κB and AP-1 activity via the JNK pathway.
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Jo
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Yuk
authors.affiliation: Konkuk University, Seoul, Republic of Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: Pusan National University, Busan, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Chungbuk Provincial College, Okcheon, Chungbuk, Republic of Korea.
authors.forename: Jae Hwang
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D054465:Peroxiredoxin VI; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2