TY - JOUR
T1 - Induction of transcription factors in human T lymphocytes by aspirin-like drugs
AU - Flescher, Eliezer
AU - Ledbetter, Jeffrey A.
AU - Ogawa, Noryoshi
AU - Vela-Roch, Norma
AU - Fossum, Donna
AU - Dang, Howard
AU - Talal, Norman
N1 - Funding Information:
1 This study was supported by PHS Grants DE-09311 and DE-10863, grants from the Research Service of the Veterans Administration, and the RGK Foundation. 2 To whom correspondence should be addressed at current address: Institute of Environmental Medicine, New York University Medical Center, Long Meadow Road, Tuxedo, NY 10987. 3 Abbreviations used: ALD, aspirin-like drugs: CAT, chloramphenicol acetyltransferase; \[Ca~+\]i,n tracellular free calcium concentration; DTT, dithiothreitol; H-7, lo(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride; HM1, human muscarinic subtype-1 receptor; MNC, mononuclear cells; mAb, monoclonal antibody; PCR, polymer-
PY - 1995
Y1 - 1995
N2 - Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2. To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCLγ1 tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NFκB, and AP-1. These binding activities are expressed only in activated T cells. The expression of AP-1 depended on calcium mobilization and PKC activation. These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD. The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors. However, the ALD stimulus is not capable of causing complete T cell activation.
AB - Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2. To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCLγ1 tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NFκB, and AP-1. These binding activities are expressed only in activated T cells. The expression of AP-1 depended on calcium mobilization and PKC activation. These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD. The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors. However, the ALD stimulus is not capable of causing complete T cell activation.
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U2 - 10.1016/0008-8749(95)80033-F
DO - 10.1016/0008-8749(95)80033-F
M3 - Article
C2 - 7720085
AN - SCOPUS:0028893253
VL - 160
SP - 232
EP - 239
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 2
ER -