Blood monocytes (MNs) transfected with serine protease inhibitor 9 (PI-9) small inhibitory RNA (siRNA) display decreased expression of Bcl-2 messenger RNA (mRNA) and increased levels of caspase 3 protein in response to stimulation with lysates of Mycobacterium tuberculosis H37Rv. A, Compared with transfection with control siRNA, transfection with PI-9 specific siRNA significantly decreased M. tuberculosis–induced expression of the antiapoptotic molecule Bcl-2 after 4 hours of incubation with H37Rv lysate. mRNA is again expressed as the percentage observed in MNs treated with PI-9 siRNA, compared the percentage in those treated with control siRNA. B, Consistent with this, MNs transfected with PI-9 specific siRNA demonstrated significantly increased production of MN caspase 3 protein (as quantified by Western blot analysis after 24 hours of incubation with H37Rv lysate), which is a common end effector of intrinsic and extrinsic apoptosis.