UP-REGULATION OF KERATIN-17 EXPRESSION IN HUMAN HACAT KERATINOCYTES BY INTERFERON-GAMMA

The immortalized human keratinocyte cell Line HaCaT was used to assess the effect of interferon-gamma (IFN-gamma) on expression of keratin K 17. Both IFN-gamma and K17 have been implicated in the pathophysiology of psoriasis. Western and quantitative enzyme-linked immunosorbent as say analyses demonstrated increasing induction of K17 protein by 48 h exposure to IFN-gamma at concentrations of 10, 50, and 250 U/ml. At 50 U/ml IFN-gamma, immunohistochemical analysis revealed numerous K17-po sitive foci, whereas in situ hybridization demonstrated K17 message in the majority of cells. In addition, at low (5 U/ml) concentrations of IFN-gamma, cell proliferation and protein synthesis decreased, as det ermined by H-3-thymidine labeling and C-14-amino acid uptake. These da ta suggest that aberrant K17 expression observed in psoriatic lesions may be a consequence of IFN-gamma overexpression, and that the HaCaT c ell line may be a useful in vitro model system to elucidate the underl ying mechanisms.