Oxidative and heat stress gene changes in hypertrophic scar fibroblasts stimulated with interleukin-1beta

Cutaneous wounds that involve loss of tissue heal through a complex process of generating granulation tissue to initially cover the wound, followed by epithelialization, and contraction. Normal healing requires a delicate balance between cellular, matrix, and vascularity build up and breakdown. Defects in the regulation of this balance can alter normal scar formation through fibroblastic hyperproliferation, which is characteristic of hypertrophic scar formation.

Primary fibroblasts cultures from hypertrophic scar or adjacent normal skin were seeded in growth medium. Half of each was stimulated with interleukin (IL)-1beta for 6 h and half served as control nonstimulated fibroblasts. Supernatants were tested for expressed proteins and the fibroblasts for changes in gene expression.

Comparison between normal skin and hypertrophic scar fibroblasts stimulated with IL-1beta indicate that 15 genes increased and 8 genes decreased expression. When normal skin was stimulated with IL-1beta, there were increases in the expression of heat shock transcription factor-1, hsp70, and IL-6 When hypertrophic scar was stimulated with IL-1beta, there was a decrease in nuclear factor-kappaB, GADD45-alpha, p53, p53 binding protein, and Cox-2 genes. These genes may play specific but different roles in controlling the cellular response to cell stress and apoptosis.

Data presented suggest that oxidative and heat stress proteins, stimulated through IL-1beta, may be important mediators of abnormal scarring.