Document Detail


IL-2 and IL-10 production by human CD4+T cells is differentially regulated by p38: mode of stimulation-dependent regulation of IL-2.
MedLine Citation:
PMID:  15249725     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antigenic stimulation of T cells initiates a complex series of intracellular signaling pathways that target and activate different cytokine genes. The participation of mitogen-activated protein kinases (MAPKs) in these processes has not been studied thoroughly and in some instances conflicting results have been reported. Here we have examined the role of p38 MAPK on IL-2 and IL-10 production following activation of human CD4+ T cells or of the leukemic cell line Hut-78, with either plate-bound anti-CD3 in the presence or absence of soluble anti-CD28 (plCD3, plCD3/sCD28), or with cross-linked anti-CD3 and anti-CD28 (crsCD3+CD28), or with PMA plus ionomycin. Pharmacological inhibition of the p38 pathway with either SB203580, SB202190, or SKF86002 strongly downregulated IL-10 production by T cells stimulated with any of the above treatments. In contrast the effect of p38 inhibition on IL-2 was stimulus dependent. Thus, p38 inhibition strongly upregulated IL-2 production (up to 10-fold) in the plCD3- and plCD3/sCD28-stimulated cultures while it had minimal or no effect in the other two stimulation protocols. Intracellular and mRNA levels of IL-2 and IL-10 were also upregulated and downregulated, respectively, by p38 inhibitors in the plCD3/sCD28-stimulated CD4+ T cells. Also, the induction of IL-2 and the parallel suppression of IL-10 by p38 inhibitors were independent of the balance between these two cytokines, as demonstrated by the addition of exogenous IL-10 or blocking anti-IL-10 antibody in CD4+ and Hut-78 cell cultures. These results show that p38 acts as a molecular switch that changes the balance between IL-2 and IL-10. This is especially important considering the opposing role of these cytokines in peripheral immune tolerance.
Authors:
Christina Veiopoulou; Olga Kogopoulou; Evaggelos Tzakos; George Mavrothalassitis; Dimitris Mitsias; Anastasia Karafoulidou; Fotini Paliogianni; Haralampos M Moutsopoulos; George Thyphronitis
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroimmunomodulation     Volume:  11     ISSN:  1021-7401     ISO Abbreviation:  Neuroimmunomodulation     Publication Date:  2004  
Date Detail:
Created Date:  2004-07-13     Completed Date:  2004-10-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9422763     Medline TA:  Neuroimmunomodulation     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  199-208     Citation Subset:  IM    
Copyright Information:
Copyright 2004 S. Karger AG, Basel
Affiliation:
Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / pharmacology
Antigens, CD28 / immunology
Antigens, CD3 / immunology
CD4-Positive T-Lymphocytes / enzymology,  immunology,  metabolism*
Cell Line, Tumor
Cells, Cultured
Down-Regulation / drug effects,  immunology
Enzyme Inhibitors / pharmacology
Humans
Interleukin-10 / biosynthesis*,  genetics,  pharmacology
Interleukin-2 / biosynthesis*,  genetics
MAP Kinase Signaling System / drug effects,  immunology
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
RNA, Messenger / drug effects,  metabolism
Up-Regulation / drug effects,  immunology
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD28; 0/Antigens, CD3; 0/Enzyme Inhibitors; 0/Interleukin-2; 0/RNA, Messenger; 130068-27-8/Interleukin-10; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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