title: DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor.
abstract: OBJECTIVE
  DJ-1-a multifunctional protein responding to oxidative stress-is a possible regulator of the inflammatory response that plays an important role in atherosclerosis. Stromal cell-derived factor (SDF)-1 and its receptor, chemokine receptor type 4 (CXCR4), have been implicated in the recruitment of inflammatory cells during atherosclerosis. Here we investigated the hypothesis that DJ-1 protein might participate in CD3+ T cell functions in response to SDF-1 and contribute to the pathogenesis of atherosclerosis.
  
  
  RESULTS
  SDF-1 stimulated migration in mouse CD3+ T cells in a dose-dependent manner. SDF-1 also elevated the phosphorylation level of extracellular-regulated kinase (ERK) 1/2 in CD3+ T cells. These SDF-1-induced responses were greater in CD3+ T cells from DJ-1 gene knockout (DJ-1(-/-)) mice than in those from wild type (DJ-1(+/+)) mice and were abolished by treatment with WZ811 and PD98059, inhibitors of CXCR4 and ERK1/2, respectively. Flow cytometry revealed that expression of the CXCR4 receptor was greater in CD3+ T cells from DJ-1(-/-) mice than in those from the controls. Moreover, expression of the CD3 protein was observed in the neointimal plaque from carotid artery-ligated mice and was stronger in DJ-1(-/-) mice compared with controls. The CD3+ T cell subsets, Th1 and Th17, showed increased production of interferon-γ and interleukin-17 in DJ-1(-/-) compared with DJ-1(+/+) mice.
  
  
  CONCLUSIONS
  DJ-1 protein is involved in the SDF-1-induced CD3+ T cell migration via overexpression of the CXCR4 receptor, and that DJ-1 acts as an inhibitory regulator in vascular remodeling such as neointima formation.
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Seung Hyo
authors: SH
authors: Jung
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Kyung Jong
authors: KJ
authors: Won
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Kang Pa
authors: KP
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Dong Hyun
authors: DH
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Suyeol
authors: S
authors: Yu
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Dong-Youb
authors: DY
authors: Lee
authors: Department of Internal Medicine, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Eun-Hye
authors: EH
authors: Seo
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Hyun
authors: H
authors: Kang
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea; Depatment of Biomedical Laboratory Science, Kyungbok University, Pochen 487-717, Republic of Korea.
authors: Eun-Seok
authors: ES
authors: Park
authors: Department of Cardiovascular Medicine, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors: Hyun-Joong
authors: HJ
authors: Kim
authors: Department of Microbiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea. Electronic address: shlee@kku.ac.kr.
authors: Seung Hyun
authors: SH
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea. Electronic address: bkkim2@kku.ac.kr.
authors: Bokyung
authors: B
authors: Kim
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12; D008297:Male; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058426:Neointima; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D000071617:Protein Deglycase DJ-1; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D017252:CD3 Complex; D054377:Chemokine CXCL12; D015513:Oncogene Proteins; D019718:Receptors, CXCR4; D054464:Peroxiredoxins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: Atherosclerotic plaque; CD3+ T cell migration; CXCR4 receptor; DJ-1; Stromal cell-derived factor -1