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The Secretion Mechanism of HMGB1 from Peripheral Blood Monocytes of Rheumatoid Arthritis Patients and the Effect of Thalidomide on It

Author: GongYanZuo
Tutor: ZuoXiaoXia
School: Central South University
Course: Internal Medicine Rheumatology
Keywords: rheumatoid arthritis peripheral blood monocytes high mobility group box chromosomal protein 1 thalidomide
CLC: R593.22
Type: Master's thesis
Year: 2007
Downloads: 57
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Abstract


Objective: To investigate the release and intracellular localization of high mobility group box chromosomal protein 1 (HMGB1) in peripheral blood monocytes of rheumatoid arthritis (RA) patients and the effect of thalidomide on them.Methods: 19 RA patients and 20 healthy controls were included in the study. Ficoll density gradient centrifugation was used to separate monocytes from peripheral blood. Monocytes were treated by 100ng/ml TNF-αor 100ng/ml TNF-αplus 40μg/ml thalidomide. The monocytes were cultured in incubator with 37℃and 5%CO2 for 24 hours. Then Western blot was applied for detection of HMGB1 in culture medium. In addition, the intracellular localization of HMGB1 in the monocytes was investigated by immunocytochemical analysis.Results: The expressions of HMGB1 protein were significantly higher in culture medium of peripheral blood monocytes from RA patients compared with healthy controls (P<0.05). The expressions of HMGB1 protein were significantly deceased in culture medium of peripheral blood monocytes from RA patients after stimulated with TNF-αand treated with thalidomide compared with only stimulated with TNF-α(P<0.05), while the expressions of HMGB1 protein were not significantly different between culture medium of peripheral blood monocytes from RA patients after stimulated with TNF-αand no stimulation(P<0.05). Nonstimulated peripheral blood monocytes of RA patients displayed a strong staining for HMGB1 in the nucleus; HMGB1 of peripheral blood monocytes of RA patients after stimulation with TNF-αappeared to move from the nucleus, which became weakly stained, to the cytoplasm, which displayed a strong staining; while the monocytes after TNF-αand thalidomide treatment displayed a stong staining for HMGB1 in the nucleus.Conclusion: TNF-αstimulation induce release and translocation of HMGB1 in peripheral blood monocytes of RA patients, and thalidomide inhibits release and translocation of HMGB1.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Rheumatoid arthritis
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