Activation of cytosolic phospholipase A2 in human T-lymphocytes involves inhibitor-kappaB and mitogen-activated protein kinases.
The group IV 85 kDa cytosolic phospholipase A(2) regulates many aspects of innate immunity. However, the function of this enzyme in T-cells remains controversial. We show here that human peripheral blood lymphocytes and Jurkat cells express cytosolic phospholipase A(2) and produce prostaglandin A(2) and leukotriene B(4). Selective inhibitors of this enzyme suppressed Ca(2+)-ionophore-, mitogen- and T-cell receptor-mediated expression of interleukin-2 at the level of transcription from the promoter. Activation of mitogen-activated protein kinases (MAPK), degradation of inhibitor-kappaBalpha and transactivation by nuclear factor-kappaB (NFkappaB) were impaired as was the antigen-, lectin- and interleukin-2-driven proliferation of T-cells in vitro. Ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma) induced rapid phosphorylation of MAPK in human monocytic but not in Jurkat cells. These data indicated that in T-cells, eicosanoids generated upon signal-activated cytosolic phospholipase A(2) promote NFkappaB-dependent interleukin-2 transcription via a PPARgamma-independent mechanism involving the MAPK-pathway.
Burgermeister
Elke
E
Department of Biological Regulation, The Weizmann Institute of Science, I-76100 Rehovot, Israel.
Endl
Josef
J
Scheuer
Werner V
WV
D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins; D015777:Eicosanoids / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000201:enzymology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; D015777:Eicosanoids; D007376:Interleukin-2; D008024:Ligands; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2