Induction of lipocortin 1 by topical steroid in rat skin.
Western blotting and densitometric analysis of extracts obtained from EDTA extraction of skin segments showed greater extracellular Lipocortin 1 (LC1) in skin sites from steroid-treated animals compared to that seen in matched vehicle treated animals. Extracellular LC1 was maximal 3 hr after steroid, less was found in skin after 6 hr and levels had returned to basal at 18 hr. Pre-treatment of rats with the glucocorticoid receptor antagonist RU38486 (20 mg/kg) prevented the steroid induction of extracellular LC1 at both the 3 and 6 hr time-points. Systemic treatment of rats with betamethasone sodium phosphate (0.1-1 mg/kg) showed that the induction of LC1 on the cell surface was both time- and dose-dependent. Oedema in rat skin caused by 5-hydroxytryptamine (5-HT), platelet activating factor (PAF) and zymosan activated serum (ZAS) was assessed using 125I-labelled human serum albumin. Following a 3 hr topical treatment with betamethasone-17-valerate the inflammatory activities of all of the tested stimuli were significantly attenuated demonstrating that at this time-point the topical steroid was biologically active. Topical steroid treatment of the skin resulted in a translocation of LC1 to the cell surface, which was maximal after a 3 hr period and was also temporally associated with the anti-inflammatory effect of these agents.
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St Bartholomew's Hospital, London, U.K.
A
A
Ahluwalia
R W
RW
Mohamed
R J
RJ
Flower
D000287:Administration, Topical; D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis* / Q000302:isolation & purification; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D004492:Edetic Acid; D008297:Male; D015735:Mifepristone; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D017305:Annexin A1; D015735:Mifepristone; D004492:Edetic Acid; D001624:Betamethasone Valerate