sq-23377 and involucrin

The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co-culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood-derived T cells were found to induce Fas-dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN-gamma. The T-cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of alpha 6-integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM-1 expression and its ligand LFA-1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas-dependent cell death signals delivered by the T cells.

Topics: Antibodies, Monoclonal; Apoptosis; Caspase 3; Caspase Inhibitors; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Transformed; Cells, Cultured; Coculture Techniques; Cysteine Proteinase Inhibitors; Fas Ligand Protein; fas Receptor; Humans; Integrin alpha6; Intercellular Adhesion Molecule-1; Interferon-gamma; Ionomycin; Keratin-10; Keratinocytes; Lymphocyte Activation; Lymphocyte Function-Associated Antigen-1; Oligopeptides; Poly(ADP-ribose) Polymerases; Protein Precursors; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha