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IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis.
J Immunol. 2000 Nov 01; 165(9):4927-34.JI

Abstract

We and others have reported that IFN-alpha potentiates the apoptotic effects of TNF through a mechanism that is not understood. Because the nuclear transcription factors NF-kappaB and AP-1 have recently been reported to mediate anti-apoptosis and cell survival, we hypothesized that IFN-alpha potentiates the cytotoxic effects of TNF by suppressing TNF-induced activation of NF-kappaB and AP-1. We tested this hypothesis by pretreating human Jurkat T cells with IFN-alpha, which blocked TNF-induced activation of NF-kappaB and AP-1 in a time- and dose-dependent manner as determined by EMSA. IFN-alpha blocked TNF-induced phosphorylation and degradation of the inhibitor subunit of NF-kappaB, and suppressed NF-kappaB and AP-1 activation induced by various other inflammatory stimuli. NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TNF receptor-associated factor 2, and NF-kappaB-inducing kinase was also abrogated by IFN-alpha pretreatment. The suppression of NF-kappaB and AP-1 correlated with the potentiation of TNF-induced cytotoxicity and caspase activation. Overall our results suggest that IFN-alpha potentiates the apoptotic effects of TNF possibly by suppressing NF-kappaB and AP-1 activation.

Authors+Show Affiliations

Cytokine Research Laboratory, Department of Bioimmunotherapy, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11046018

Citation

Manna, S K., et al. "IFN-alpha Suppresses Activation of Nuclear Transcription Factors NF-kappa B and Activator Protein 1 and Potentiates TNF-induced Apoptosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 165, no. 9, 2000, pp. 4927-34.
Manna SK, Mukhopadhyay A, Aggarwal BB. IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis. J Immunol. 2000;165(9):4927-34.
Manna, S. K., Mukhopadhyay, A., & Aggarwal, B. B. (2000). IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis. Journal of Immunology (Baltimore, Md. : 1950), 165(9), 4927-34.
Manna SK, Mukhopadhyay A, Aggarwal BB. IFN-alpha Suppresses Activation of Nuclear Transcription Factors NF-kappa B and Activator Protein 1 and Potentiates TNF-induced Apoptosis. J Immunol. 2000 Nov 1;165(9):4927-34. PubMed PMID: 11046018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis. AU - Manna,S K, AU - Mukhopadhyay,A, AU - Aggarwal,B B, PY - 2000/10/25/pubmed PY - 2001/2/28/medline PY - 2000/10/25/entrez SP - 4927 EP - 34 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 165 IS - 9 N2 - We and others have reported that IFN-alpha potentiates the apoptotic effects of TNF through a mechanism that is not understood. Because the nuclear transcription factors NF-kappaB and AP-1 have recently been reported to mediate anti-apoptosis and cell survival, we hypothesized that IFN-alpha potentiates the cytotoxic effects of TNF by suppressing TNF-induced activation of NF-kappaB and AP-1. We tested this hypothesis by pretreating human Jurkat T cells with IFN-alpha, which blocked TNF-induced activation of NF-kappaB and AP-1 in a time- and dose-dependent manner as determined by EMSA. IFN-alpha blocked TNF-induced phosphorylation and degradation of the inhibitor subunit of NF-kappaB, and suppressed NF-kappaB and AP-1 activation induced by various other inflammatory stimuli. NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TNF receptor-associated factor 2, and NF-kappaB-inducing kinase was also abrogated by IFN-alpha pretreatment. The suppression of NF-kappaB and AP-1 correlated with the potentiation of TNF-induced cytotoxicity and caspase activation. Overall our results suggest that IFN-alpha potentiates the apoptotic effects of TNF possibly by suppressing NF-kappaB and AP-1 activation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11046018/IFN_alpha_suppresses_activation_of_nuclear_transcription_factors_NF_kappa_B_and_activator_protein_1_and_potentiates_TNF_induced_apoptosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11046018 DB - PRIME DP - Unbound Medicine ER -