Document Detail

Distinct roles for p42/p44 and p38 mitogen-activated protein kinases in the induction of IL-2 by IL-1.
MedLine Citation:
PMID:  10479400     Owner:  NLM     Status:  MEDLINE    
Interleukin 1 (IL-1) activates p42/p44 and p38 mitogen-activated protein kinases (MAP kinases) in target cells. Here we have used two specific inhibitors, PD98059 which inhibits MAP kinase kinase (MEK), and SB203580 which inhibits p38 MAP kinase to explore the involvement of these kinases in the induction of IL-2 by IL-1 in the murine thymoma cell line EL4.NOB-1. Both kinase inhibitors suppressed IL-1-stimulated IL-2 production. PD98059 blocked IL-2 mRNA accumulation and the induction of a reporter gene linked to the IL-2 promoter. In contrast, SB203580 only marginally inhibited IL-2 promoter-linked reporter gene expression and had no inhibitory effect on IL-2 mRNA levels. Neither PD98059 nor SB203580 had an inhibitory effect on NFkappaB-driven reporter gene expression in response to IL-1. Surprisingly, higher concentrations of SB203580 (30 microM) potentiated the IL-1 responses. PD98059 also inhibited induction of IL-2 by phorbol 12-myristate 13-acetate (PMA), and AP1-linked reporter gene expression in response to PMA but not IL-1. These results indicate that p42/p44 MAP kinase is involved in the regulation of IL-2 gene transcription by IL-1, whilst p38 MAP kinase has a post-transcriptional target. Additional IL-1 signalling pathways can clearly compensate for the lack of p38 MAP kinase which result in potentiation of the IL-1 responses observed at high-dose SB203580.
J S Matthews; L A O'Neill
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cytokine     Volume:  11     ISSN:  1043-4666     ISO Abbreviation:  Cytokine     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-21     Completed Date:  1999-10-21     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  643-55     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Department of Biochemistry, Trinity College, Dublin 2, Ireland.
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MeSH Terms
Amino Acid Sequence
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors,  physiology*
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Gene Expression Regulation / drug effects*
Genes, Reporter
Imidazoles / pharmacology
Interleukin-1 / pharmacology*
Interleukin-2 / biosynthesis*,  genetics
Mitogen-Activated Protein Kinase 1 / physiology*
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases*
Molecular Sequence Data
NF-kappa B / physiology
Protein Kinase Inhibitors
Pyridines / pharmacology
Signal Transduction / drug effects
Tetradecanoylphorbol Acetate / pharmacology
Thymoma / pathology
Thymus Neoplasms / pathology
Transcription Factor AP-1 / physiology
Tumor Cells, Cultured / drug effects
p38 Mitogen-Activated Protein Kinases
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Interleukin-1; 0/Interleukin-2; 0/NF-kappa B; 0/Protein Kinase Inhibitors; 0/Pyridines; 0/SB 203580; 0/Transcription Factor AP-1; 16561-29-8/Tetradecanoylphorbol Acetate; EC Protein Kinases; EC Protein Kinase 1; EC Protein Kinases; EC Mitogen-Activated Protein Kinases; EC Protein Kinase Kinases

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