GLUCOCORTICOIDS INHIBIT KERATINOCYTE GROWTH-FACTOR PRODUCTION IN PRIMARY DERMAL FIBROBLASTS

The participation of growth factors in wound healing and tissue repair has been well established. Previous studies demonstrated that the exp ression of keratinocyte growth factor (KGF) was greatly elevated short ly after injury and that topical application of KGF accelerated healin g. Steroidal antiinflammatory agents, specifically glucocorticoids, ma rkedly impair wound healing. The participation of KGF in wound healing led us to examine the effect of glucocorticoids on KGF production. Th e addition of dexamethasone significantly reduced the level of constit utively produced KGF messenger RNA, protein, and bioactivity in condit ioned medium from dermal fibroblasts. This inhibitory effect was obser ved with a variety of glucocorticoids, whereas nonsteroidal antiinflam matory compounds had little effect on KGF synthesis. The mechanisms by which dexamethasone decreased KGF production include a combination of a diminished transcriptional Fate and destabilization of the KGF mess enger RNA. Cytokines such as interleukin-1 alpha, platelet-derived gro wth factor-BB, and transforming growth factor-alpha, typically up-regu lated during wound healing, augment KGF expression by dermal fibroblas ts. We determined that dexamethasone also blocked this inductive effec t. These results suggest that glucocorticoids could inhibit KGF produc tion in the setting of wound repair, which may contribute to the impai r ment of healing associated with glucocorticoid use.