T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes.

Schafer, P H; Wang, L; Wadsworth, S A; Davis, J E; Siekierka, J J

Schafer, P H; Wang, L; Wadsworth, S A; Davis, J E; Siekierka, J J.

Afiliación

Schafer PH; Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.

J Immunol ; 162(2): 659-68, 1999 Jan 15.

Article en En | MEDLINE | ID: mdl-9916683

RESUMEN

p38 mitogen-activated protein kinase (MAPK) (p38) is involved in various cellular responses, including LPS stimulation of monocytes, resulting in production of proinflammatory cytokines such as TNF-alpha. However, the function of p38 during antigenic stimulation of T cells is largely unknown. Stimulation of the human Th cell clone HA-1.70 with either the superantigen staphylococcal enterotoxin B (SEB) or with a specific antigenic peptide resulted in p38 activation and the release of TNF-alpha. MAPK-activated protein kinase-2 (MAPKAPK-2), an in vivo substrate for p38, was also activated by T cell signaling. SB 203580, a selective inhibitor of p38, blocked p38 and MAPKAPK-2 activation in the T cell clone but did not completely inhibit TNF-alpha release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-alpha production by the clone. In human peripheral T cells, p38 was not activated by SEB, but rather by CD28 cross-linking, whereas in the human leukemic T cell line Jurkat, p38 was activated by CD3 and CD28 cross-linking in an additive fashion. TNF-alpha production by peripheral T cells in response to SEB and anti-CD28 mAb correlated more closely with ERK activity than with p38 activity. Therefore, various forms of T cell stimulation can activate the p38 pathway depending on the cells examined. Furthermore, unlike LPS-stimulated monocytes, TNF-alpha production by T cells is only partially p38-dependent.

Asunto(s)

Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo; Lipopolisacáridos/inmunología; Activación de Linfocitos; Proteínas Quinasas Activadas por Mitógenos; Monocitos/inmunología; Transducción de Señal/inmunología; Linfocitos T/inmunología; Factor de Necrosis Tumoral alfa/biosíntesis; Regulación hacia Arriba/inmunología; Anticuerpos Monoclonales/metabolismo; Antígenos CD28/sangre; Antígenos CD28/inmunología; Antígenos CD28/fisiología; Calcineurina/fisiología; Proteínas Quinasas Dependientes de Calcio-Calmodulina/fisiología; Células Clonales/enzimología; Células Clonales/inmunología; Células Clonales/metabolismo; Enterotoxinas/farmacología; Activación Enzimática/inmunología; Antígenos de Histocompatibilidad Clase II/farmacología; Humanos; Células Jurkat; Activación de Macrófagos; Monocitos/metabolismo; Staphylococcus aureus/inmunología; Superantígenos/farmacología; Linfocitos T/enzimología; Linfocitos T/metabolismo; Factor de Necrosis Tumoral alfa/metabolismo; Proteínas Quinasas p38 Activadas por Mitógenos

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Monocitos / Linfocitos T / Transducción de Señal / Regulación hacia Arriba / Lipopolisacáridos / Factor de Necrosis Tumoral alfa / Proteínas Quinasas Dependientes de Calcio-Calmodulina / Proteínas Quinasas Activadas por Mitógenos Límite: Humans Idioma: En Revista: J Immunol Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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