title: Chemokine Signaling Pathway Involved in CCL2 Expression in Patients with Rheumatoid Arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Chemokines are involved in RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involved in the activation of CCL2 production in collagen-induced arthritis rat ST.
  
  
  METHODS
  Total RNA was isolated from PB leukocytes and synovium of the knee joint in both RA patients and control populations. Real-time polymerase chain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically.
  
  
  RESULTS
  The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST.
  
  
  CONCLUSIONS
  CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targeting this signaling pathway may provide a novel therapeutic avenue in RA.
authors.affiliation: School of Dentistry, Tianjin Medical University, Tianjin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: School of Dentistry, Tianjin Medical University, Tianjin, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Infection and Rheumatology, General Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: Center of Joint Surgery, Tianjin Hospital, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center of Joint Surgery, Tianjin Hospital, Tianjin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Infection, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yang
authors.affiliation: School of Dentistry, Tianjin Medical University, Tianjin, China.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Dentistry, Tianjin Medical University, Tianjin, China. zy66@vip.sina.com.
authors.forename: Changyi
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood* / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D012333:RNA, Messenger
keywords: CCL2; arthritis; leukocytes; rheumatoid; synovial membrane