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Title: Nucleophosmin may act as an alarmin: Implications for severe sepsis
Authors: Yuko Nawa
Ko Ichi Kawahara
Salunya Tancharoen
Xiaojie Meng
Hisayo Sameshima
Takashi Ito
Yoshiki Masuda
Hitoshi Imaizumi
Teruto Hashiguchi
Ikuro Maruyama
Kagoshima University Faculty of Medicine
Mahidol University
Sapporo Medical University School of Medicine
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-Sep-2009
Citation: Journal of Leukocyte Biology. Vol.86, No.3 (2009), 645-653
Abstract: NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell-cycle progression, apoptosis, cell differentiation, and sensing cellular stress. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. In the present work, stimulation of cells with the alarmin-inducible molecule endotoxin, for 16 h, resulted in NPM release into the culture supernatants of RAW264.7 cells, a murine macrophage cell line. Extracellular NPM was detected in the ascites of the CLP model. NPM was translocated into the cytoplasm from the nucleus in LPS -stimulated RAW264.7 cells; furthermore, NPM was detected in the cytosols of infiltrated macrophages in the CLP model. rNPM induced release of proinflammatory cytokines, TNF-α, IL-6, and MCP-1, from RAW264.7 cells and increased the expression level of ICAM-1 in HUVECs. NPM induced the phosphorylation of MAPKs in RAW264.7 cells. Our data indicate that NPM may have potent biological activities that contribute to systemic inflammation. Further investigations of the role of NPM may lead to new therapies for patients with septic shock or other inflammatory diseases. © Society for Leukocyte Biology.
ISSN: 07415400
Appears in Collections:Scopus 2006-2010

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