Monocyte Chemotactic Protein-1 (MCP-1) mRNA is Down-Regulated in Human Dermal Fibroblasts by Dexamethasone: Differential Regulation by TGF-β

Abstract

Macrophages are a source of cytokines driving repair. Wound macrophages are derived from circulating monocytes. Monocyte chemotactic protein-1 (MCP-1) is a potent specific monocyte chemoattractant. Treatment of serum stimulated dermal fibroblasts with dexamethasone led to a dose dependent down-regulation of MCP-1 mRNA levels. Such an anti-inflammatory effect may partially explain the negative influence of glucocorticoid treatment on wound repair. Topical or parenteral treatment with TGF-β restores healing rates in glucocorticoid treated animals. Treatment of fibroblasts cultured in serum free media with TGF-β increased MCP-1 mRNA levels. TGF-β treatment of fibroblasts cultured in serum also partially overcame the dexamethasone mediated decrease in MCP-1 mRNA levels. In glucocorticoid treated animals TGF-β may stimulate repair by an indirect pro-inflammatory action following transcriptional up-regulation of MCP-1.

Key Words:

• wound healing
• transforming growth factor beta
• monocyte chemotactic protein-1
• dexamethasone