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 J.
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.
UR - http://www.scopus.com/inward/record.url?scp=0033556260&partnerID=8YFLogxK
M3 - Article
C2 - 9916683
AN - SCOPUS:0033556260
SN - 0022-1767
VL - 162
SP - 659
EP - 668
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -