A pilot study of estrogen's effects on bronchial myocyte adhesion molecule expression.
We examined the effects of estrogen on tumor necrosis factor alpha (TNF-alpha)-induced expression of intracellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) in cultured human bronchial smooth muscle cells (BSMC). Experiments were performed in triplicate in T-75 tissue culture flasks containing normal human BSMC. Four experiments were carried out: untreated BSMC cells (control); TNF-alpha 1000 U/ml stimulation of BSMC; forskolin 5 microM before TNF-alpha stimulation of BSMC; and estradiol 30 microM before TNF-alpha stimulation of BSMC. Cyclic adenosine monophosphate was measured by a commercially available radioimmunoassay kit. Cell expression of ICAM-1 and VCAM-1 was quantified by flow cytometry Incubation of cells with TNF-alpha 1000 U/ml for 24 hours elicited a 27-fold increase in basal expression of ICAM-1 and a 2-fold increase in VCAM-1 (p>0.05). Incubation of BSMC with forskolin 5 microM, for 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 62% and VCAM-1 slightly by 17%. The BSMC incubated with estradiol 30 microM, 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 21%; VCAM-1 remained unchanged (p>0.05). We found a trend toward inhibition of TNF-alpha-stimulated ICAM-1 expression in cultured BSMC with pretreatment with estradiol. However, due to large variability within the cell culture model, statistical significance was not reached.
Dickens
G R
GR
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington 40515, USA.
Matheny
C J
CJ
Morris
P E
PE
Clifton
G D
GD
Ensom
M H
MH
D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010865:Pilot Projects; D011863:Radioimmunoassay; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; D004958:Estradiol; D000242:Cyclic AMP