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Induction of Serine Protease Inhibitor 9 by Mycobacterium Tuberculosis Inhibits Apoptosis and Promotes Survival of Infected Macrophages

Induction of Serine Protease Inhibitor 9 by Mycobacterium Tuberculosis Inhibits Apoptosis and Promotes Survival of Infected Macrophages

Zahra Toossi, Mianda Wu, Roxana Rojas, Barbara Kalsdorf, Htin Aung, Christina S Hirsch, Jessica Walrath, Angela Wolbink, Marieke van Ham, Richard F Silver

J Infect Dis. 2012 Jan 1;205(1):144-51.

PMID: 22090449

Abstract:

Our recent microarray analysis of infected human alveolar macrophages (AMs) found serine protease inhibitor 9 (PI-9) to be the most prominently expressed of a cluster of apoptosis-associated genes induced by virulent Mycobacterium tuberculosis. In the current study, we show that induction of PI-9 occurs within hours of infection with M. tuberculosis H37Rv and is maintained through 7 days of infection in both AMs and blood monocytes. Inhibition of PI-9 by small inhibitory RNA decreased M. tuberculosis-induced expression of the antiapoptotic molecule Bcl-2 and resulted in a corresponding increase in production of caspase 3, a terminal effector molecule of apoptosis. Further, PI-9 small inhibitory RNA mediated a significant reduction in the subsequent survival of M. tuberculosis within AMs. Thus PI-9 induction within human mononuclear phagocytes by virulent M. tuberculosis serves to protect these primary targets of infection from elimination by apoptosis and thereby promotes intracellular survival of the organism.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1622426134	Serine Hydrolase Inhibitor-9		1622426-13-4	Price

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