Pharmacological modification of 12-0-tetradecanoylphorbol-13-acetate induced inflammation and epidermal cell proliferation in mouse skin.
Topical application of TPA to mouse skin causes oedema (2-6 h) neutrophil influx (3-24 h) and epidermal cell proliferation (24-48 h). Topical application of a cyclooxygenase inhibitor (indomethacin) dual cyclooxygenase and lipoxygenase inhibitors (phenidone and BW755C) a selective lipoxygenase inhibitor (AA861), protein synthesis inhibitors (cycloheximide and actinomycin D) or a glucocorticosteroid (prednisolone) inhibited oedema and neutrophil influx. Systemic administration of an inhibitor of microtubule assembly (colchicine) also prevented neutrophil influx and oedema. These results suggest that the inflammatory response to TPA depends on an interaction between a protein and products of arachidonic acid metabolism to produce a neutrophil dependent oedema. Epidermal cell proliferation was inhibited by topical administration of prednisolone, indomethacin, BW755C and cycloheximide but not systemically administered methotrexate. This suggests that inhibition of the early inflammatory response to TPA prevents the subsequent epidermal proliferation.
Griffiths
R J
RJ
Department of Pharmacology, Fisons plc - Pharmaceutical Division, Loughborough, Leicestershire.
Wood
B E
BE
Li
S
S
Blackham
A
A
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology*; D015232:Dinoprostone / Q000378:metabolism; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004817:Epidermis / Q000473:pathology*; D005260:Female; D016859:Lipoxygenase Inhibitors; D051379:Mice; D009504:Neutrophils; D011239:Prednisolone / Q000494:pharmacology; D014176:Protein Biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011239:Prednisolone; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D003078:Colchicine