090 Effect of Cytokines and Heat Shock on Human β‐Defensin‐2 Levels in Cultured Keratinocytes

Abstract

Burns have been associated with high levels of circulating pro‐inflammatory cytokines which promote systemic inflammatory response syndrome (SIRS), immunosuppression and sepsis for which no effective treatment is currently available. Defensins, a family of cationic naturally occurring antimicrobial peptides are considered important components of the innate immune system and enhance adaptive immunity. We have examined the effects of pro‐inflammatory cytokines, interleukin 1β‐(IL‐1β), gamma‐interferon (IFNγ) and tumor necrosis factor‐α(TNFα) on human β‐defensin‐2 (HBD‐2) levels in cultured keratinocytes. We have also examined the effects of heat shock at 42 °C. Our results demonstrate that only TNFα shows significant induction of HBD‐2 but this induction was not sustained in the long term. In addition, endogenous levels of defensin were significantly reduced by exposure to heat shock. The keratinocytes also responded to IL‐1β by becoming hypertrophic. These results indicate that stress‐related, pro‐inflammatory cytokines can induce keratinocytes to synthesize HBD‐2, while heat shock appears to reduce its production. Understanding the roles cytokines play in the continued problems associated with severe wounding, and in particular, major burn injury, is important. This study provides further insight into the role of natural anti‐microbial peptides under conditions of stress.