CYTOKINE-INDUCED ICAM-1 EXPRESSION IN HUMAN KERATINOCYTES IS HIGHLY VARIABLE IN KERATINOCYTE STRAINS FROM DIFFERENT DONORS

Induction of intercellular adhesion molecule 1 (ICAM-1) expression in the epidermis is felt to be an important initiator of leukocyte/keratinocyte interactions in many inflammatory skin diseases. The purpose of this project was to determine the individual variability of cytokine-induced ICAM-1 expression in human keratinocytes obtained from different donors. In 55 different keratinocyte strains, there was significant individual variability in ICAM-1 expression by either tumor necrosis factor a (TNF-alpha) or interferon-gamma. There was no correlation (r = 0.266, p = 0.06) in response of the same strain to either TNF-alpha or interferon-gamma. Multiple (n = 22) keratinocyte strains showed no significant induction of ICAM-`1 expression to IL-1. The level of ICAM-1 expression in response to TNF-alpha and ultraviolet radiation (UVR) in individual strains was highly correlated in three different comparisons: level of stimulated response versus baseline (TNF-alpha and UVR both p < 0.0001); stimulation index TNF-alpha versus UVR (p = 0.00947); and variability of stimulated response versus variability of baseline (TNF p < 0.001; UVR p = 0.002). UVR-induced release of TNF from keratinocytes also showed variability among different keratinocyte strains. The UVR-induced ICAM-1. response in human keratinocytes and transformed epithelial cell was variably blocked with anti-TNF antibodies. The release of TNF from keratinocytes by UVR and the individually variable but linked characteristics of UVR and TNF-alpha stimulated ICAM-1 expression support the hypothesis that TNF-alpha is a major mediator of UVR-induced ICAM-1 expression.