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.