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IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis.
J Immunol. 1998 Sep 15; 161(6):2863-72.JI

Abstract

IL-13 is known to suppress the production of inflammatory cytokines such as TNF. Whether IL-13 also modulates the biologic effects of TNF is not known. In the present report we examined the effect of IL-13 on TNF-induced activation of nuclear transcription factors NF-kappa B and activation protein-1 (AP-1) and apoptosis. Pretreatment of cells with IL-13 blocked TNF-induced NF-kappa B activation, nuclear translocation of p65 subunit, and degradation of I kappa B alpha. IL-13 also inhibited NF-kappa B activation by LPS, okadaic acid, H2O2, and ceramide. TNF-induced NF-kappa B-dependent gene transcription was also blocked by IL-13. TNF-induced activation of another nuclear transcription factor, AP-1, was suppressed by IL-13. The activation of N-terminal c-Jun kinase and mitogen-activated protein kinase kinase, implicated in the regulation of AP-1 and NF-kappa B, was also down-regulated by IL-13. TNF-mediated cytotoxicity and activation of caspase-3 were abolished by IL-13. The inhibitory effects of IL-13 on TNF were sensitive to H-7, neomycin, and wortmannin, suggesting that the pathway consisting of protein kinase C, phosphatidylinositol 3-kinase, and phospholipase C must be involved in IL-13 signaling. Thus, overall, these results demonstrate that IL-13 is a potent inhibitor of TNF-mediated activation of NF-kappa B, AP-1, and apoptosis, which may contribute to its previously described immunosuppressive and anti-inflammatory effects.

Authors+Show Affiliations

Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9743347

Citation

Manna, S K., and B B. Aggarwal. "IL-13 Suppresses TNF-induced Activation of Nuclear Factor-kappa B, Activation Protein-1, and Apoptosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 6, 1998, pp. 2863-72.
Manna SK, Aggarwal BB. IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. J Immunol. 1998;161(6):2863-72.
Manna, S. K., & Aggarwal, B. B. (1998). IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. Journal of Immunology (Baltimore, Md. : 1950), 161(6), 2863-72.
Manna SK, Aggarwal BB. IL-13 Suppresses TNF-induced Activation of Nuclear Factor-kappa B, Activation Protein-1, and Apoptosis. J Immunol. 1998 Sep 15;161(6):2863-72. PubMed PMID: 9743347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. AU - Manna,S K, AU - Aggarwal,B B, PY - 1998/9/22/pubmed PY - 1998/9/22/medline PY - 1998/9/22/entrez SP - 2863 EP - 72 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 161 IS - 6 N2 - IL-13 is known to suppress the production of inflammatory cytokines such as TNF. Whether IL-13 also modulates the biologic effects of TNF is not known. In the present report we examined the effect of IL-13 on TNF-induced activation of nuclear transcription factors NF-kappa B and activation protein-1 (AP-1) and apoptosis. Pretreatment of cells with IL-13 blocked TNF-induced NF-kappa B activation, nuclear translocation of p65 subunit, and degradation of I kappa B alpha. IL-13 also inhibited NF-kappa B activation by LPS, okadaic acid, H2O2, and ceramide. TNF-induced NF-kappa B-dependent gene transcription was also blocked by IL-13. TNF-induced activation of another nuclear transcription factor, AP-1, was suppressed by IL-13. The activation of N-terminal c-Jun kinase and mitogen-activated protein kinase kinase, implicated in the regulation of AP-1 and NF-kappa B, was also down-regulated by IL-13. TNF-mediated cytotoxicity and activation of caspase-3 were abolished by IL-13. The inhibitory effects of IL-13 on TNF were sensitive to H-7, neomycin, and wortmannin, suggesting that the pathway consisting of protein kinase C, phosphatidylinositol 3-kinase, and phospholipase C must be involved in IL-13 signaling. Thus, overall, these results demonstrate that IL-13 is a potent inhibitor of TNF-mediated activation of NF-kappa B, AP-1, and apoptosis, which may contribute to its previously described immunosuppressive and anti-inflammatory effects. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9743347/IL_13_suppresses_TNF_induced_activation_of_nuclear_factor_kappa_B_activation_protein_1_and_apoptosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9743347 DB - PRIME DP - Unbound Medicine ER -