Effects of cytokines and heat shock on defensin levels of 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. This study examines 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 also examined the effects of heat shock at 42 °C. The 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. These experiments give us further insight into the role of natural antimicrobial peptides under conditions of stress.