Abstract
Corticotropin-releasing hormone (CRH) has been shown to inhibit proliferation and modulate expression of inflammation markers in the epidermal cells. In the present study we report that CRH also stimulates nuclear factor-kappa B (NF-kappaB) activity. Incubation with CRH of human keratinocytes derived from primary cultures resulted in increased binding of DNA by NF-kappaB. CRH induced translocation of NF-kappaB subunit p65 from the cytoplasm to the nucleus and induced expression of kappaB-driven chloramphenicol acetyltransferase (CAT) reporter gene. NF-kappaB translocation was accompanied by degradation of the inhibitor of NF-kappaB alpha (IkappaB-alpha). Specificity of the CRH effect was demonstrated by the use of CRH-R antagonists antalarmin and alpha-helical CRH [9-41]. CRH-dependent stimulation of NF-kappaB activity is consistent with accumulated data about role of this neuropeptide in the regulation of local epidermal homeostasis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Blotting, Western / methods
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Calcium-Binding Proteins*
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Cell Nucleus / metabolism
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Cells, Cultured
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Chloramphenicol O-Acetyltransferase / genetics
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Corticotropin-Releasing Hormone / pharmacology*
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Cytoplasm / metabolism
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DNA / metabolism
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Electrophoretic Mobility Shift Assay
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Gene Expression / drug effects
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Genes, Reporter
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Humans
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I-kappa B Proteins / analysis
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I-kappa B Proteins / metabolism
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Keratinocytes / metabolism*
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Membrane Glycoproteins / metabolism
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Microscopy, Confocal
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NF-kappa B / metabolism*
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Nerve Tissue Proteins / metabolism
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Peptide Fragments / pharmacology
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Pyrimidines / pharmacology
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Pyrroles / pharmacology
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Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
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Stimulation, Chemical
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Synaptotagmin I
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Synaptotagmins
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Translocation, Genetic
Substances
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Calcium-Binding Proteins
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I-kappa B Proteins
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Membrane Glycoproteins
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NF-kappa B
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Nerve Tissue Proteins
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Peptide Fragments
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Pyrimidines
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Pyrroles
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Receptors, Corticotropin-Releasing Hormone
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Synaptotagmin I
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antalarmin
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Synaptotagmins
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DNA
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Corticotropin-Releasing Hormone
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corticotropin releasing hormone (9-41)
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Chloramphenicol O-Acetyltransferase