STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease Journal Article

   

Authors:	Lu, S. X.; Alpdogan, O.; Lin, J.; Balderas, R.; Campos-Gonzalez, R.; Wang, X.; Gao, G. J.; Suh, D.; King, C.; Chow, M.; Smith, O. M.; Hubbard, V. M.; Bautista, J. L.; Cabrera-Perez, J.; Zakrzewski, J. L.; Kochman, A. A.; Chow, A.; Altan-Bonnet, G.; van den Brink, M. R. M.
Article Title:	STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease
Abstract:	Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation, and donor T cells are indispensable for GVHD. Current therapies have limited efficacy, selectivity, and high toxicities. We used a novel flow cytometry technique for the analysis of intracellular phosphorylation events in single cells in murine BMT models to identify and validate novel GVHD drug targets.1-7 This method circumvents the requirement for large numbers of purified cells, unlike western blots. We defined a signaling profile for alloactivated T cells in vivo and identified the phosphorylation of ERK1/2 and STAT-3 as important events during T-cell (allo)activation in GVHD. We establish that interference with STAT-3 phosphorylation can inhibit T-cell activation and proliferation in vitro and GVHD in vivo. This suggests that phospho-specific flow cytometry is useful for the identification of promising drug targets, and ERK1/2 and STAT-3 phosphorylation in alloactivated T cells may be important for GVHD. © 2008 by The American Society of Hematology.
Keywords:	controlled study; protein phosphorylation; transplantation, homologous; unclassified drug; nonhuman; flow cytometry; cd8+ t lymphocyte; cell proliferation; t lymphocyte; t-lymphocytes; mouse; animal; metabolism; animals; mice; stat3 protein; animal experiment; animal model; allogenic bone marrow transplantation; in vivo study; in vitro study; phosphorylation; immunology; lymphocyte activation; cd4+ t lymphocyte; western blotting; cell subpopulation; graft versus host reaction; mitogen activated protein kinase 1; mitogen activated protein kinase 3; stat3 transcription factor; bone marrow transplantation; graft vs host disease; t lymphocyte activation; allotransplantation; mitogen-activated protein kinase 3; 2 (2 amino 3 methoxyphenyl)chromone; alpha [amino(4 aminophenylthio)methylene] 2 (trifluoromethyl)phenylacetonitrile; cucurbitacin; cucurbitacin e; cucurbitacin i; stat3 protein, mouse
Journal Title:	Blood
Volume:	112
Issue:	13
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2008-12-15
Start Page:	5254
End Page:	5258
Language:	English
DOI:	10.1182/blood-2008-03-147322
PUBMED:	18838616
PROVIDER:	scopus
PMCID:	PMC2597618
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-58149401207&partnerID=40&md5=afbd80d226916e93f88e2557040fb732
Notes:	--- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"

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