Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 293, Issue 6, Pages C1916-C1923Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00293.2007
Keywords
NF-kappa B; activator protein-1; STAT1; TNF-alpha; IFN-gamma
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Histamine enhances the production of human beta-defensin-2 in human keratinocytes. Am J Physiol Cell Physiol 293: C1916-C1923, 2007. First published October 10, 2007; doi: 10.1152/ajpcell.00293.2007. -The anti-microbial peptide human beta-defensin-2 (hBD-2), produced by epidermal keratinocytes, plays pivotal roles in anti- microbial defense, inflammatory dermatoses, and wound repair. hBD-2 induces histamine release from mast cells. We examined the in vitro effects of histamine on hBD-2 production in normal human keratinocytes. Histamine enhanced TNF-alpha-or IFN-gamma-induced hBD-2 secretion and mRNA expression. Histamine alone enhanced transcriptional activities of NF-kappa B and activator protein-1 (AP-1) and potentiated TNF-alpha-induced NF-kappa B and AP-1 activities or IFN-alpha-induced NF-kappa B and STAT1 activities. Antisense oligonucleotides against NF-kappa B components p50 and p65, AP- 1 components c- Jun and c- Fos, or H1 antagonist pyrilamine suppressed hBD- 2 production induced by histamine plus TNF- alpha or IFN-gamma. Antisense oligonucleotide against STAT1 only suppressed hBD- 2 production induced by histamine plus IFN-gamma. Histamine induced serine phosphorylation of inhibitory NF-kappa B alpha ( I kappa B alpha) alone or together with TNF-alpha or IFN-gamma. Histamine induced c- Fos mRNA expression alone or together with TNF-alpha, whereas it did not further increase c- Jun mRNA levels enhanced by TNF-gamma. Histamine induced serine phosphorylation of STAT1 alone or together with IFN-alpha, whereas it did not further enhance IFN-gamma- induced tyrosine phosphorylation of STAT1. The histamine- induced serine phosphorylation of STAT1 was suppressed by MAPKK (MEK) inhibitor PD98059. These results suggest that histamine stimulates H1 receptor and potentiates TNF-alpha-or IFN-gamma-induced hBD-2 production dependent on NF-kappa B, AP-1, or STAT1 in human keratinocytes. Histamine may potentiate anti- microbial defense, skin inflammation, and wound repair via the induction of hBD-2.
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