202 (1), 41-50――This study was designed to determine the roles of STAT1 protein in defense against mycobacterial infection. Airborne infection of STAT1 knockout (KO) mice with a Mycobacterium tuberculosis Kurono strain induced multiple necrotic lesions in lungs, spleen and liver, while that in wild-type (WT) mice did not. The STAT1 KO mice succumbed to mycobacterial infection by the 35 th day after infection. Compared with the levels in WT mice, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α, interferon-γand IL-12 mRNA levels were significantly lower in the lung of STAT1 KO mice. Interestingly, granulomatous lesion development in STAT1 KO mice was inhibited significantly by treatment with exogenous recombinant murine IL-12. Therefore, STAT1 regulates IL-12 expression and appears to be a critical transcription factor in controling mycobacterial infection.――――STAT1; M. tuberculosis; STAT1 knockout mouse; IL-12© 2004 Tohoku University Medical Press

Activation mechanisms of signal transducer and activator of transcription (STAT) was clarified in the biological responsive system stimulated with interferon (IFN)-γ. STAT family consists of seven transcription factors (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6)(Darnell 1997). STAT proteins are cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. Among them, STAT1 is activated by stimuli with IFN-α/βand IFN-γand is essential for cell growth suppression in response to