Bing-Hua Wang1,2,3, Yi-Hua Lu1,3, Long-Fei Wu1,3, Xin Lu1,3, Wei Guo1,3, Fei-Yan Deng1,3, Shu-Feng Lei4,5. 1. Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, People's Republic of China. 2. Department of Epidemiology and Health Statistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China. 3. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, People's Republic of China. 4. Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, People's Republic of China. leisf@suda.edu.cn. 5. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, People's Republic of China. leisf@suda.edu.cn.
Abstract
OBJECTIVES: The cytokines play critical roles in the complex pathogenesis of rheumatoid arthritis (RA), but the specific cytokines are still in need of being discovered. This multi-stage study was performed to identify novel RA cytokines in plasma and further understand the pathological mechanism of the identified cytokines. METHOD: The plasma cytokine protein profile was evaluated by using Human Cytokine Antibody Array 440 in 18 subjects (RA: healthy control = 9:9). Then, enzyme-linked immunosorbent assay (ELISA) was used to validate the highlighted cytokines in 80 subjects (RA: healthy control = 40:40). Further functional experiments on fibroblast-like synoviocytes were performed to identify the pathological mechanisms of the highlighted cytokines for RA. RESULTS: A total of seven significant cytokines have differential expressions between RA patients and controls (fold change (FC) > 2, P value < 0.05). The difference in plasma for the highlighted platelet-derived growth factor (PDGF)-BB was validated in an independent validation sample (P = 0.005). Further, the PDGF-BB obviously promotes cell proliferation of MH7A cell, probably by inhibiting cell apoptosis and accelerating the cell cycle. The PDGF-BB can also promote MH7A cell migration. CONCLUSIONS: This study evaluated the plasma cytokine protein array profile associated with RA and highlighted the importance of PDGF-BB. PDGF-BB has an important role in RA-FLS proliferation and migration. These results suggest that PDGF-BB might contribute to occurrence and development of RA. Key Points • The levels of plasma cytokines were systemically tested using Human Cytokine Antibody Arrays. • The expression difference of PDGF-BB was validated in an independent sample. • PDGF-BB obviously promotes cell proliferation and migration in RA-FLS.
OBJECTIVES: The cytokines play critical roles in the complex pathogenesis of rheumatoid arthritis (RA), but the specific cytokines are still in need of being discovered. This multi-stage study was performed to identify novel RA cytokines in plasma and further understand the pathological mechanism of the identified cytokines. METHOD: The plasma cytokine protein profile was evaluated by using Human Cytokine Antibody Array 440 in 18 subjects (RA: healthy control = 9:9). Then, enzyme-linked immunosorbent assay (ELISA) was used to validate the highlighted cytokines in 80 subjects (RA: healthy control = 40:40). Further functional experiments on fibroblast-like synoviocytes were performed to identify the pathological mechanisms of the highlighted cytokines for RA. RESULTS: A total of seven significant cytokines have differential expressions between RA patients and controls (fold change (FC) > 2, P value < 0.05). The difference in plasma for the highlighted platelet-derived growth factor (PDGF)-BB was validated in an independent validation sample (P = 0.005). Further, the PDGF-BB obviously promotes cell proliferation of MH7A cell, probably by inhibiting cell apoptosis and accelerating the cell cycle. The PDGF-BB can also promote MH7A cell migration. CONCLUSIONS: This study evaluated the plasma cytokine protein array profile associated with RA and highlighted the importance of PDGF-BB. PDGF-BB has an important role in RA-FLS proliferation and migration. These results suggest that PDGF-BB might contribute to occurrence and development of RA. Key Points • The levels of plasma cytokines were systemically tested using Human Cytokine Antibody Arrays. • The expression difference of PDGF-BB was validated in an independent sample. • PDGF-BB obviously promotes cell proliferation and migration in RA-FLS.
Authors: Annemarie L M A Jansen; Irene van der Horst-Bruinsma; Dirkjan van Schaardenburg; Rob J van de Stadt; Margret H M T de Koning; Ben A C Dijkmans Journal: J Rheumatol Date: 2002-10 Impact factor: 4.666
Authors: R Lafyatis; N L Thompson; E F Remmers; K C Flanders; N S Roche; S J Kim; J P Case; M B Sporn; A B Roberts; R L Wilder Journal: J Immunol Date: 1989-08-15 Impact factor: 5.422