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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/19684
Title: C-reactive protein induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells
Authors: Ko ichi Kawahara
Kamal Krishna Biswas
Masako Unoshima
Takashi Ito
Kiyoshi Kikuchi
Yoko Morimoto
Masahiro Iwata
Salunya Tancharoen
Yoko Oyama
Kazunori Takenouchi
Yuko Nawa
Noboru Arimura
Meng Xiao Jie
Binita Shrestha
Naoki Miura
Toshiaki Shimizu
Kentaro Mera
Shin ichiro Arimura
Noboru Taniguchi
Hideo Iwasaka
Sonshin Takao
Teruto Hashiguchi
Ikuro Maruyama
Kagoshima University
Oita University Faculty of Medicine
Mahidol University
Keywords: Medicine
Issue Date: 1-May-2008
Citation: Cardiovascular Pathology. Vol.17, No.3 (2008), 129-138
Abstract: Background: C-reactive protein (CRP) is widely used as a sensitive biomarker for inflammation. Increasing evidence suggests that CRP plays a role in inflammation. High-mobility group box-1 (HMGB1), a primarily nuclear protein, is passively released into the extracellular milieu by necrotic or damaged cells and is actively secreted by monocytes/macrophages. Extracellular HMGB1 as a potent inflammatory mediator has stimulated immense curiosity in the field of inflammation research. However, the molecular dialogue implicated between CRP and HMGB1 in delayed inflammatory processes remains to be explored. Methods and results: The levels of HMGB1 in culture supernatants were determined by Western blot analysis and enzyme-linked immunosorbent assay in macrophage RAW264.7 cells. Purified CRP induced the release of HMGB1 in a dose- and time-dependent fashion. Immunofluorescence analysis revealed nuclear translocation of HMGB1 in response to CRP. The binding of CRP to the Fcγ receptor in RAW264.7 cells was confirmed by fluorescence-activated cell sorter analysis. Pretreatment of cells with IgG-Fc fragment, but not IgG-Fab fragment, efficiently blocked this binding. CRP triggered the activation of p38MAPK and ERK1/2, but not Jun N-terminal kinase. Moreover, both p38MAPK inhibitor SB203580 and small interfering RNA significantly suppressed the release of HMGB1, but not the MEK1/2 inhibitor U-0126. Conclusion: We demonstrated for the first time that CRP, a prominent risk marker for inflammation including atherosclerosis, could induce the active release of HMGB1 by RAW264.7 cells through Fcγ receptor/p38MAPK signaling pathways, thus implying that CRP plays a crucial role in the induction, amplification, and prolongation of inflammatory processes, including atherosclerotic lesions. © 2008 Elsevier Inc. All rights reserved.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=42949085762&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/19684
ISSN: 10548807
Appears in Collections:Scopus 2006-2010

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