Effects of cytokines and heat shock on defensin levels of cultured keratinocytes.
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-1beta (IL-1beta), gamma-interferon (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) on human beta-defensin-2 (HBD-2) levels in cultured keratinocytes. We also examined the effects of heat shock at 42 degrees C. The results demonstrate that only TNFalpha 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-1beta 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.
Bick
Roger J
RJ
The Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Poindexter
Brian J
BJ
Bhat
Satyanarayan
S
Gulati
Salil
S
Buja
Maximilian
M
Milner
Stephen M
SM
D048429:Cell Size / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D018869:Heat-Shock Response / Q000276:immunology*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D023083:beta-Defensins / Q000378:metabolism*
D016207:Cytokines; C106641:DEFB4A protein, human; D023083:beta-Defensins