Corticotropin-releasing hormone inhibits nuclear factor-kappaB pathway in human HaCaT keratinocytes.
Treatment of human HaCaT keratinocytes with corticotropin-releasing hormone modulates cell proliferation and expression of inflammation markers. In this study we report that corticotropin-releasing hormone also inhibits nuclear factor-kappaB binding and transcriptional activity. Incubating cells in the absence of growth factors increased nuclear factor-kappaB activity; this effect was significantly attenuated by corticotropin-releasing hormone. Specifically, corticotropin-releasing hormone downregulated p50/p50 and p50/p65 dimers of nuclear factor-kappaB, diminished kappaB-driven CAT reporter gene activity and inhibited IkappaB-beta degradation. Moreover, corticotropin-releasing hormone inhibited the trans-cription of the nuclear factor-kappaB responsive genes, interleukin-2 and heat shock protein 90.
Zbytek
Blazej
B
Department of Histology and Immunology, Medical University of Gdansk, Gdansk, Poland.
Pfeffer
Lawrence M
LM
Slominski
Andrzej T
AT
D015153:Blotting, Western; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D018841:HSP90 Heat-Shock Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007376:Interleukin-2; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D003346:Corticotropin-Releasing Hormone; D015500:Chloramphenicol O-Acetyltransferase