Ascorbic Acid, Ultraviolet C Rays, and Glucose but not Hyperthermia Are Elicitors of Humanβ-Defensin 1 mRNA in Normal Keratinocytes

Abstract

Hosts’ innate defense systems are upregulated by antimicrobial peptide elicitors (APEs). Our aim was to investigate the effects of hyperthermia, ultraviolet A rays (UVA), and ultraviolet C rays (UVC) as well as glucose and ascorbic acid (AA) on the regulation of humanβ-defensin 1 (DEFB1), cathelicidin (CAMP), and interferon-γ(IFNG) genes in normal human keratinocytes (NHK). The indirectin vitroantimicrobial activity againstStaphylococcus aureusandListeria monocytogenesof these potential APEs was tested. We found that AA is a more potent APE forDEFB1than glucose in NHK. Glucose but not AA is an APE forCAMP. Mild hypo- (35°C) and hyperthermia (39°C) are not APEs in NHK. AA-dependentDEFB1upregulation below 20 mM predictsin vitroantimicrobial activity as well as glucose- and AA-dependentCAMPandIFNGupregulation. UVC upregulatesCAMPandDEFB1genes but UVA only upregulates theDEFB1gene. UVC is a previously unrecognized APE in human cells. Our results suggest that glucose upregulatesCAMPin an IFN-γ-independent manner. AA is an elicitor of innate immunity that will challenge the current concept of late activation of adaptive immunity of this vitamin. These results could be useful in designing new potential drugs and devices to combat skin infections.