THE STATE OF DIFFERENTIATION OF CULTURED HUMAN KERATINOCYTES DETERMINES THE LEVEL OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) EXPRESSION INDUCED BY GAMMA-INTERFERON

Inducing the expression of ICAM-1 (CD54) on the surface of epidermal keratinocytes is an important step in initiating leukocyte interaction with the epidermis. We studied the effect of keratinocyte differentiation and of drugs used to treat epidermal inflammation on the induction of this important adhesion molecule. Cell membrane expression of ICAM-1 in cultured human keratinocytes was analyzed using both immunofluorescence and FACS analysis of staining with anti-ICAM-1 monoclonal antibody and was correlated with markers of keratinocyte differentiation. Cell-surface ICAM-1 expression was induced by gamma-interferon in all culture conditions, but was significantly greater (p < 0.014) in cells grown in low-calcium medium ([Ca++] 0.03 mM), and correlated with increased staining for the basal cell keratin K5. The synthetic retinoid Etretin (Ro 101670) enhanced the interferon-induced ICAM-1 expression over a wide concentration range (10(-8) - 10(-5) M); however, this effect was only seen in the more differentiated cells grown in 0. 15 mM and 1.0 mM calcium and not in the cells grown in 0.03 mM calcium. The Etretin effects on intracellular K5 staining paralleled those on cell-surface ICAM-1. Anti-inflammatory glucocorticoids had no effect on ICAM-1 expression in cultured human keratinocytes, even at suboptimal gamma-interferon doses (5 U/ml). Beta-estradiol, on the other hand, mimicked the Etretin effect, increasing both IFN induction of ICAM-1 expression and K5 staining in more differentiated keratinocytes in 0.15 and 1.0 mM calcium, but not in those in 0.03 mM calcium. Both Etretin and beta-estradiol decreased staining of involucrin, a marker of terminal differentiation, supporting the proposition that in this experimental system these drugs suppress keratinocyte differentiation. The enhanced ICAM-1 induction in keratinocytes with a basal level of differentiation correlates with the in vivo effects of interferon on ICAM-1 and may be a principal determinant in the patterns of ICAM-1 seen in inflammatory skin diseases.