7552
title and abstract
High-glucose environment enhanced oxidative stress and increased interleukin-8 secretion from keratinocytes: New insights on impaired diabetic wound healing.
Impaired wound healing frequently occurs in patients with diabetes. Interluekin-8 (IL-8) production by keratinocyte is responsible for recruiting neutrophils during healing. Intense inflammation is associated with diabetic wounds while reduction of neutrophil infiltration is associated with enhanced healing. We hypothesized that increased neutrophil recruitment by keratinocytes may contribute to the delayed healing of diabetic wound. Using cultured human keratinocytes and diabetic rat model, the current study showed that high-glucose environment enhanced IL-8 production via epidermal growth factor receptor (EGFR) -extracelluar signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes. In addition, diabetic rat skin showed enhanced EGFR, ERK and IL-8 expression as compared to control rats. The dermal neutrophil infiltration of the wound, as represented by expression of myeloperoxidase level, was also significantly higher in diabetic rats. Treating diabetic rats with dapsone, an agent known to inhibit neutrophil function, was associated with improved healing. In conclusion, IL-8 production and neutrophil infiltration are increased in high-glucose environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin. Targeting these dysfunctions may present novel therapeutic approaches.