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Titolo:
Cannabinol-mediated inhibition of nuclear factor-kappa B, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes
Autore:
Herring, AC; Kaminski, NE;
Indirizzi:
Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA Michigan State Univ E Lansing MI USA 48824 xicol, E Lansing, MI 48824 USA Michigan State Univ, Dept Pathol, E Lansing, MI 48824 USA Michigan State Univ E Lansing MI USA 48824 athol, E Lansing, MI 48824 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 291, anno: 1999,
pagine: 1156 - 1163
SICI:
0022-3565(199912)291:3<1156:CIONFB>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENYLATE-CYCLASE; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; TRANSCRIPTIONAL ACTIVITY; CELL-LINE; C-REL; KINASE; EXPRESSION; RECEPTOR; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Kaminski, NE Michigan State Univ, Dept Pharmacol & Toxicol, 315 Food Safety & Toxicol Bldg, E Lansing, MI 48824 USA Michigan State Univ 315 Food Safety & Toxicol Bldg E Lansing MI USA 48824
Citazione:
A.C. Herring e N.E. Kaminski, "Cannabinol-mediated inhibition of nuclear factor-kappa B, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes", J PHARM EXP, 291(3), 1999, pp. 1156-1163

Abstract

Cannabinol (CBN), an immunosuppressive cannabinoid and ligand for the peripheral cannabinoid receptor CB2, inhibits the cAMP signaling cascade in forskolin-stimulated thymocytes. The objective of the present studies was to further characterize the mechanism of CBN immune modulation by investigatingits effects on interleukin-2 (IL-2) secretion, cAMP response element (CRE), and kappa B DNA binding activity in phorbol ester (phorbol-12-myristate-13-acetate, PMA) plus calcium ionophore (PMA/Io)-activated thymocytes. PMA/Io treatment induced CRE and kB DNA binding activity that was attenuated in the presence of CBN. A concomitant and concentration-related inhibition of IL-2 also was produced by CBN in PMA/Io-activated thymocytes. PMA/Io induced two CRE DNA binding complexes, a major complex consisting of a cAMP response element-binding protein (CREB)-1 homodimer, and a minor CREB-1/activating transcription factor (ATF)-2 complex. Both CRE complexes were inhibited by CBN. Conversely, two kappa B DNA binding complexes were observed, but only one was PMA/Io-inducible. However, the DNA binding activity of both complexes was diminished in the presence of CBN. The PMA/Io-inducible kappa B complex was a p65/c-Rel heterodimer. Analysis of up-stream regulation revealed a decrease in phosphorylated CREB/ATF nuclear proteins in PMA/Io-activated thymocytes after CBN treatment. Similarly, CBN prevented the phosphorylation-dependent degradation of the nuclear factor-kappa B inhibitory proteinI kappa B-alpha. These results provide a potential link between the CBN-mediated inhibition of thymocyte function, including IL-2 production, and theinhibition of two critical transcription factor families, CREB/ATF and NF-kappa B/Rel.

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Documento generato il 20/09/20 alle ore 22:49:40