Monocyte chemotactic protein-1 (MCP-1) mRNA is down-regulated in human dermal fibroblasts by dexamethasone: differential regulation by TGF-beta.
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 of fibroblasts cultured in serum free media with TGF-beta increased MCP-1 mRNA levels. TGF-beta treatment of fibroblasts cultured in serum also partially overcame the dexamethasone mediated decrease in MCP-1 mRNA levels. In glucocorticoid treated animals TGF-beta may stimulate repair by an indirect pro-inflammatory action following transcriptional up-regulation of MCP-1.
Slavin
J
J
Department of Surgery, University of California, San Francisco 94143, USA.
Unemori
E
E
Hunt
T K
TK
Amento
E
E
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001345:Autoradiography; D001769:Blood; D015152:Blotting, Northern; D002455:Cell Division; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003907:Dexamethasone