Cytokine-induced ICAM-1 expression in human keratinocytes is highly variable in keratinocyte strains from different donors

Abstract

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-α) or interferon-γ. There was no correlation (r = 0.266, p 0.06) in response of the same strain to either TNF-α or interferon-γ. 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-α and ultraviolet radiation (WR) in individual strains was highly correlated in three different comparisons: level of stimulated response versus baseline (TNF-α and UVR both p < 0.0001); stimulation index TNF-α 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 TNP 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-TNP antibodies. The release of TNF from keratinocytes by UVR and the individually variable but linked characteristics of UVR and TNF-α stimulated ICAM-1 expression support the hypothesis that TNF-α is a major mediator of UVR-induced ICAM-1 expression.