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Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents.
J Immunol. 1998 Sep 15; 161(6):2873-80.JI

Abstract

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide found mainly in the brain, pituitary, and circulation. It inhibits most forms of inflammation by a mechanism that is not known. As most types of inflammation require activation of NF-kappa B, we investigated the effect of alpha-MSH on the activation of this transcription factor by a wide variety of inflammatory stimuli. Electrophoretic mobility shift assay showed that alpha-MSH completely abolished TNF-mediated NF-kappa B activation in a dose- and time-dependent manner. It also suppressed NF-kappa B activation induced by LPS, okadaic acid, and ceramide. The effect was specific, as the activation of the transcription factor activating protein-1 by TNF was unaffected. Western blot analysis revealed that TNF-dependent degradation of the inhibitory subunit of NF-kappa B, I kappa B alpha, and nuclear translocation of the p65 subunit of NF-kappa B were also inhibited. This correlated with suppression of NF-kappa B-dependent reporter gene expression induced by TNF. The inhibitory effect of alpha-MSH appeared to be mediated through generation of cAMP, as inhibitors of adenylate cyclase and of protein kinase A reversed its inhibitory effect. Similarly, addition of membrane-permeable dibutyryl cAMP, like alpha-MSH, suppressed TNF-induced NF-kappa B activation. Overall, our results suggest that alpha-MSH suppresses NF-kappa B activated by various inflammatory agents and that this mechanism probably contributes to its 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

9743348

Citation

Manna, S K., and B B. Aggarwal. "Alpha-melanocyte-stimulating Hormone Inhibits the Nuclear Transcription Factor NF-kappa B Activation Induced By Various Inflammatory Agents." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 6, 1998, pp. 2873-80.
Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol. 1998;161(6):2873-80.
Manna, S. K., & Aggarwal, B. B. (1998). Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. Journal of Immunology (Baltimore, Md. : 1950), 161(6), 2873-80.
Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating Hormone Inhibits the Nuclear Transcription Factor NF-kappa B Activation Induced By Various Inflammatory Agents. J Immunol. 1998 Sep 15;161(6):2873-80. PubMed PMID: 9743348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. AU - Manna,S K, AU - Aggarwal,B B, PY - 1998/9/22/pubmed PY - 1998/9/22/medline PY - 1998/9/22/entrez SP - 2873 EP - 80 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 161 IS - 6 N2 - Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide found mainly in the brain, pituitary, and circulation. It inhibits most forms of inflammation by a mechanism that is not known. As most types of inflammation require activation of NF-kappa B, we investigated the effect of alpha-MSH on the activation of this transcription factor by a wide variety of inflammatory stimuli. Electrophoretic mobility shift assay showed that alpha-MSH completely abolished TNF-mediated NF-kappa B activation in a dose- and time-dependent manner. It also suppressed NF-kappa B activation induced by LPS, okadaic acid, and ceramide. The effect was specific, as the activation of the transcription factor activating protein-1 by TNF was unaffected. Western blot analysis revealed that TNF-dependent degradation of the inhibitory subunit of NF-kappa B, I kappa B alpha, and nuclear translocation of the p65 subunit of NF-kappa B were also inhibited. This correlated with suppression of NF-kappa B-dependent reporter gene expression induced by TNF. The inhibitory effect of alpha-MSH appeared to be mediated through generation of cAMP, as inhibitors of adenylate cyclase and of protein kinase A reversed its inhibitory effect. Similarly, addition of membrane-permeable dibutyryl cAMP, like alpha-MSH, suppressed TNF-induced NF-kappa B activation. Overall, our results suggest that alpha-MSH suppresses NF-kappa B activated by various inflammatory agents and that this mechanism probably contributes to its anti-inflammatory effects. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9743348/Alpha_melanocyte_stimulating_hormone_inhibits_the_nuclear_transcription_factor_NF_kappa_B_activation_induced_by_various_inflammatory_agents_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9743348 DB - PRIME DP - Unbound Medicine ER -