title: Upregulated expression of CCR3 in rheumatoid arthritis and CCR3-dependent activation of fibroblast-like synoviocytes.
abstract: It is recognized that CC chemokine receptor 3 (CCR3) is associated with numerous inflammatory conditions and fibroblast-like synoviocyte (FLS) invasiveness correlates with articular damage in rheumatoid arthritis (RA). However, little is known of the expression and action of CCR3 on FLS in RA. In the present study, we investigated the expression of CCR3 on dispersed synovial tissue and peripheral blood cells in RA and influence of eotaxin-1 on FLS functions by using flow cytometry analysis, FLS challenge, and real-time PCR techniques. The results showed that approximately 7.0 % dispersed synovial cells are CCR3+ cells. Among those CCR3+ cells, 38.1, 23.8, and 20.6 % cells are CD90+CD14-CD3- (representing FLS), CD14+, and CD8+ cells, respectively, indicating that FLS is one of the major populations of CCR3+ cells in the synovial tissue of RA. In peripheral blood, CD14+ CCR3+ cells are elevated, but CD8+CCR3+ cells are reduced in RA. It was found that eotaxin-1 induced upregulated expression of CCR3 and matrix metalloproteinase (MMP)-9 messenger RNAs (mRNAs) in FLS. Since an antagonist of CCR3 suppressed the action of eotaxin-1, the event appeared CCR3 dependent. Moreover, we observed that interleukin (IL)-1β induced markedly enhanced eotaxin-1 release from FLS, but TNF-α reduced eotaxin-1 release at 12 and 24 h following incubation. In conclusion, enhanced expression of CCR3 on synovial cells and increased levels of eotaxin-1 in plasma and synovial fluid (SF) of RA indicate that CCR3-mediated mechanisms may play an important role in RA. Blockage of eotaxin-1 provoked CCR3 and MMP-9 expression in FLS by antagonist of CCR3, implicating that anti-CCR3 agents may have therapeutic use for RA.
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors: Xin
authors: X
authors: Liu
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China. zhanghuiyun2003@126.com.
authors: Huiyun
authors: H
authors: Zhang
authors: Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
authors: Xin
authors: X
authors: Chang
authors: Department of Orthopaedics, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu, 210029, China.
authors: Jirong
authors: J
authors: Shen
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors: Wenjiao
authors: W
authors: Zheng
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors: Yanan
authors: Y
authors: Xu
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors: Junling
authors: J
authors: Wang
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors: Wei
authors: W
authors: Gao
authors: Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China. shoahenghe@hotmail.com.
authors: Shaoheng
authors: S
authors: He
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000473:pathology; D054413:Chemokine CCL11 / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054397:Receptors, CCR3 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D000070918:Synoviocytes / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D053583:Interleukin-1beta; D012333:RNA, Messenger; D054397:Receptors, CCR3; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9
keywords: CCR3; Eotaxin-1; Fibroblast-like synoviocyte; IL-1β; MMP-9