Construction and characterization of the HMGB1 mutant as a competitive antagonist to HMGB1 induced cytokines release |
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Authors: | Yuan Zhiqiang Chen Jing Zhang Yan Peng Yizhi |
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Affiliation: | a Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China b Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China |
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Abstract: | Recent studies indicate that the High Mobility Group Box-1 protein (HMGB1) acts as a potent proinflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. The proinflammatory cytokine activity of HMGB1 has become a therapeutic target. In this study, we cloned the cDNA encoding human HMGB1 and constructed HMGB1 mutants using a one-step opposite direction PCR. The binding of the HMGB1 mutants to THP-1 cell and the cytokine activities of these HMGB1 mutants were observed. Results showed that the HMGB1 Mut (102-105), one of the HMGB1 mutants, in which amino acids 102-105 (FFLF) were replaced with two Glys, significantly decreased the full-length HMGB1 protein induced TNF-α release in human monocyte cultures. The results indicate that we have developed a novel recombinant HMGB1 mutant that competitively antagonizes the proinflammatory activity of HMGB1. This may be of significant importance in providing a new anti-inflammatory strategy for the treatment of severe sepsis and other inflammatory disorders. |
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Keywords: | HMGB1 Mutant Antagonist Cytokine Monocyte Inflammation |
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