IRT-1, A NOVEL INTERFERON-GAMMA-RESPONSIVE TRANSCRIPT ENCODING A GROWTH-SUPPRESSING BASIC LEUCINE-ZIPPER PROTEIN

Interferon-gamma (IFN-gamma) inhibits proliferation of vascular smooth muscle cells (VSMCs) in culture and reduces arterial restenosis post- balloon angioplasty. The identification and characterization of IFN-ga mma-specific transcripts in VSMCs are an important approach to discern the molecular mechanisms underlying vascular proliferative disease. I n this report, we describe IRT-1, a novel mRNA transcript constitutive ly expressed in a number of human tissues, but expressed in human VSMC s only when they are stimulated with IFN-gamma. This mRNA expression i s induced >200-fold 72 h after IFN-gamma treatment. IRT-1 mRNA is also acutely expressed in rat carotid arteries that are injured by balloon angioplasty. The IRT-1 cDNA transcript encodes a basic protein that c ontains a leucine zipper motif, a core nuclear localization sequence, and a single strongly hydrophobic region, Constitutive IRT-1 mRNA expr ession in human peripheral blood lymphocytes is reduced when these cel ls are stimulated to proliferate. Overexpression of IRT-1 protein in V SMCs alters their morphology and dramatically reduces their proliferat ive capacity. This study suggests that IRT-1 is an IFN-gamma-inducible factor that may regulate the progression of vascular proliferative di seases.