Activation of cytosolic phospholipase A2 in human T-lymphocytes involves inhibitor-κB 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 Ca2+-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 (PPAR-gamma) 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 A2 promote NFkappaB-dependent interleukin-2 transcription via a PPAR-gamma-independent mechanism involving the MAPK-pathway. (C) 2003 Elsevier Science B.V. All rights reserved.