Characterization of a glucocorticoid receptor and the direct effect of dexamethasone on herpes simplex virus infection of rabbit corneal cells in culture.
Homogenates prepared from a previously established cell line derived from rabbit cornea contain a macromolecule with many properties of a glucocorticoid receptor, namely high affinity (KD = 6 x 10(-9)M) and saturable capacity (135 femtomoles/mg protein) for dexamethasone, extreme heat lability, and a pattern of competition similar to that found in other glucocorticoid target cells. Intact cells specifically bind dexamethasone with an affinity similar to that found in homogenates, and the amount of steroid bound at saturation is approximately 60,000 molecules of dexamethasone per cell. Specific dexamethasone binding was found to be localized to the cell nucleus. The corneal cells were susceptible to infection with herpes simplex virus (HSV). Dexamethasone increased cell susceptibility to the virus and facilitated the spread of the infection throughout the corneal cell culture. This effect was observed at concentrations of dexamethasone as low as 10(-9) M. Tetrahydrocortisol, an inactive glucocorticoid metabolite that does not compete with dexamethasone binding to the receptor, did not enhance HSV infection at a high concentration (10(-5) M). This study demonstrates a direct effect of dexamethasone on corneal cell-HSV interaction in the absence of exogenous immunologic factors. This effect of dexamethasone may be mediated by the glucocorticoid receptor.
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D007635:Keratitis, Dendritic / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000378:metabolism* / Q000502:physiology; D011987:Receptors, Steroid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone