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

Peter H. Schafer, Liwen Wang, Scott A. Wadsworth, Janet E. Davis, John Siekierka

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Abstract

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-α. 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-α. MAPK-activated protein kinase-2 (MAPKAPK-2) 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-α release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-α 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-α 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-α production by T cells is only partially p38- dependent.

Original languageEnglish
Pages (from-to)659-668
Number of pages10
JournalJournal of Immunology
Volume162
Issue number2
StatePublished - 15 Jan 1999

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p38 Mitogen-Activated Protein Kinases
Monocytes
Up-Regulation
T-Lymphocytes
Clone Cells
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Kinase 1
Superantigens
Mitogen-Activated Protein Kinases
Protein Kinases
Cytokines
Cell Line
Peptides
staphylococcal enterotoxin B

Cite this

@article{eb165320cb784236966203879c0aacea,
title = "T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-α production in a manner distinct from LPS activation of monocytes",
abstract = "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-α. 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-α. MAPK-activated protein kinase-2 (MAPKAPK-2) 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-α release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-α 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-α 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-α production by T cells is only partially p38- dependent.",
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T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-α production in a manner distinct from LPS activation of monocytes. / Schafer, Peter H.; Wang, Liwen; Wadsworth, Scott A.; Davis, Janet E.; Siekierka, John.

In: Journal of Immunology, Vol. 162, No. 2, 15.01.1999, p. 659-668.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-α production in a manner distinct from LPS activation of monocytes

AU - Schafer, Peter H.

AU - Wang, Liwen

AU - Wadsworth, Scott A.

AU - Davis, Janet E.

AU - Siekierka, John

PY - 1999/1/15

Y1 - 1999/1/15

N2 - 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-α. 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-α. MAPK-activated protein kinase-2 (MAPKAPK-2) 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-α release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-α 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-α 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-α production by T cells is only partially p38- dependent.

AB - 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-α. 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-α. MAPK-activated protein kinase-2 (MAPKAPK-2) 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-α release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-α 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-α 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-α production by T cells is only partially p38- dependent.

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JF - Journal of Immunology

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