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Conditional up‐regulation of IL‐2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity
Author(s) -
Kogkopoulou Olga,
Tzakos Evaggelos,
Mavrothalassitis George,
Baldari Cosima T.,
Paliogianni Fotini,
Young Howard A.,
Thyphronitis George
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0705418
Subject(s) - biology , p38 mitogen activated protein kinases , mapk/erk pathway , microbiology and biotechnology , production (economics) , mitogen activated protein kinase , immunology , kinase , microeconomics , economics
The p38 mitogen‐activated protein kinase regulates many cellular processes in almost all eukaryotic cell types. In T cells, p38 was shown to regulate thymic development and cytokine production. Here, the role of p38 on interleukin‐2 (IL‐2) production by human peripheral blood CD4 + T cells was examined. When T cells were stimulated under weak stimulation conditions, pharmaceutical and molecular p38 inhibitors induced a dramatic increase of IL‐2 production. In contrast, IL‐2 levels were not affected significantly when strong stimulation was provided to T cells. The increase in IL‐2 production, following p38 inhibition, was associated with a strong up‐regulation of extracellular signal‐regulated kinase (Erk)1/2 activity. Furthermore the Erk inhibitor U0126 was able to counteract the effect of p38 inhibition on IL‐2 production, supporting the conclusion that p38 mediates its effect through Erk. These results suggest that the p38 kinase, through its ability to control Erk activation levels, acts as a gatekeeper, which prevents inappropriate IL‐2 production. Also, the finding that p38 acts in a strength‐of‐stimulation‐dependent way provides an explanation for previously reported, contradictory results regarding the role of this kinase in IL‐2 expression.