Adrenergic mediation of TNF alpha-stimulated ICAM-1 expression on human brain microvascular endothelial cells.
Adrenergic innervation derived from locus ceruleus has been implicated in regulating BBB permeability and inflammatory responses associated with neurological disorders. This report demonstrates that adrenergic agents attenuate the tumor necrosis factor-alpha (TNF alpha)-induced expression of intercellular adhesion molecule-1 (ICAM-1) on cerebral microvascular endothelial cells (HBMEC) derived from human brains. HBMEC were incubated with isoproterenol (1-10 microM) alone or in the presence of propranolol (10 microM) for 30 min followed by the addition of various concentrations of TNF alpha. ICAM-1 expression on cultured HBMEC was dose-dependently upregulated by TNF alpha. Incubation with isoproterenol significantly reduced levels of ICAM-1 expression indicating the possible involvement of adrenergic agents on ICAM-1 expression. Treatment with propranolol (beta 1/beta 2-adrenergic antagonist) and butoxamine (beta 2-adrenergic antagonist), but not atenolol (beta 1-adrenergic antagonist) reversed this inhibitory effect. Isoproterenol also dose-dependently stimulated cAMP production (assayed by RIA) by HBMEC; propranolol treatment abolished this effect. These data show that the beta 2-adrenergic receptor/cAMP pathway may be partly involved in TNF alpha-stimulated ICAM-1 expression and indicate the possible involvement of adrenergic mediation of capillary function including BBB integrity.
Ohara
Y
Y
Resuscitative Medicine Department, Naval Medical Research Center, Silver Spring, MD, USA.
McCarron
R M
RM
Hoffman
T T
TT
Sugano
H
H
Bembry
J
J
Lenz
F A
FA
Spatz
M
M
D000320:Adrenergic Fibers / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000502:physiology; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008125:Locus Coeruleus / Q000503:physiopathology*; D008833:Microcirculation / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1