Τίτλος:
Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © Society for Leukocyte Biology.
Συγγραφείς:
Kogkopoulou, O.
Tzakos, E.
Mavrothalassitis, G.
Baldari, C.T.
Paliogianni, F.
Young, H.A.
Thyphronitis, G.
Περιοδικό:
Journal of Leukocyte Biology
Εκδότης:
Federation of American Societies for Experimental Biology
Λέξεις-κλειδιά:
4 (4 fluorophenyl) 2 (4 hydroxyphenyl) 5 (4 pyridyl)imidazole; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; 4 ethyl 2 (4 methoxyphenyl) 5 (4 pyridyl)imidazole; 6 (4 fluorophenyl) 2,3 dihydro 5 (4 pyridyl)imidazo[2,1 b]thiazole; cytokine; imidazole derivative; interleukin 2; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; ribonuclease; synaptophysin; uo 126; enzyme inhibitor; interleukin 2; mitogen activated protein kinase; mitogen activated protein kinase p38, article; CD4 lymphocyte count; controlled study; cytokine production; dose response; drug inhibition; enzyme linked immunosorbent assay; enzyme phosphorylation; human; human cell; human experiment; normal human; priority journal; reverse transcription polymerase chain reaction; signal transduction; T lymphocyte; upregulation; Western blotting; biosynthesis; CD4+ T lymphocyte; cell culture; cell line; drug antagonism; drug effect; enzyme activation; enzymology; feedback system; gene expression regulation; genetics; immunology; metabolism; phosphorylation; promoter region; upregulation, Eukaryota; Pyronia tithonus, CD4-Positive T-Lymphocytes; Cell Line; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Feedback, Biochemical; Gene Expression Regulation; Humans; Interleukin-2; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Promoter Regions (Genetics); Signal Transduction; Up-Regulation
