p38 mitogen- activated protein (MAP) kinase defines a .subgroup of the mammalian MAP kinase family which is induced in response to various stimuli, such as physicochemical stress, and treatment with proinflarmnatory cytokines. However, the function of p38 in the regulation of I' cell responses has not been thoroughly examined. Therefore, we have, examined the activity of p38 follow ing T cell receptor (TCR) mediated signaling, using the human T cell clone IIA-1.70 or human T cells freshly isolated from peripheral blood. Here wr demonstrate that stimulation of clone HA-1.70 with either specific antigen or the superantigen Staphylococcal Enterotoxin B (SKB) leads to p38 activation and the release of Tumor Necrosis Factor IT (TNFrv). MAP kinase activated protein kinase-2 (MAPKAPK-2), a substrate of p;t8 m nro. is also activated by T cell signaling. This activation ran be blocked by CycSosporin A. a potent inhibitor of TCH-mediated signal transduction. Freshly isolated peripheral T cells can also be stimulated to activate the p38 pathway and release TNFa. We also demonstrate that a specific p38 inhibitor blocks p3H and MAPKAPK-2 activation in the T cell, but does not inhibit T cell production of TNFa. This is in contrast to TNFa production by human monocytes, where inhibition of p38 activity prevents TNFa production. Therefore, T cell activation signals can activate p38, but it appears that activation is not absolutely required for TNFo release.
|State||Published - 1 Dec 1997|