title: Glucocorticoids inhibit keratinocyte growth factor production in primary dermal fibroblasts.
abstract: The participation of growth factors in wound healing and tissue repair has been well established. Previous studies demonstrated that the expression of keratinocyte growth factor (KGF) was greatly elevated shortly after injury and that topical application of KGF accelerated healing. Steroidal antiinflammatory agents, specifically glucocorticoids, markedly impair wound healing. The participation of KGF in wound healing led us to examine the effect of glucocorticoids on KGF production. The addition of dexamethasone significantly reduced the level of constitutively produced KGF messenger RNA, protein, and bioactivity in conditioned medium from dermal fibroblasts. This inhibitory effect was observed with a variety of glucocorticoids, whereas nonsteroidal antiinflammatory compounds had little effect on KGF synthesis. The mechanisms by which dexamethasone decreased KGF production include a combination of a diminished transcriptional rate and destabilization of the KGF messenger RNA. Cytokines such as interleukin-1 alpha, platelet-derived growth factor-BB, and transforming growth factor-alpha, typically up-regulated during wound healing, augment KGF expression by dermal fibroblasts. We determined that dexamethasone also blocked this inductive effect. These results suggest that glucocorticoids could inhibit KGF production in the setting of wound repair, which may contribute to the impairment of healing associated with glucocorticoid use.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892 USA. chedidm@dc37a.nci.nih.gov
authors.forename: M
authors.initials: M
authors.lastname: Chedid
authors.forename: J R
authors.initials: JR
authors.lastname: Hoyle
authors.forename: K G
authors.initials: KG
authors.lastname: Csaky
authors.forename: J S
authors.initials: JS
authors.lastname: Rubin
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
chemical_list: C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D005938:Glucocorticoids; D006133:Growth Substances; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D051523:Fibroblast Growth Factor 7; D000077214:Becaplermin; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D006854:Hydrocortisone