TRIM22 enhances staurosporine-induced apoptosis in monocytes (IRM7P.492)

Abstract

Abstract Background TRIM22 was first identified as an interferon-induced gene, and constitutively expressed in peripheral blood leukocytes and lymphoid tissues, especially expressed at high levels in monocytes. Researches suggest that TRIM22 may have an impact on monocyte fate in immune response. However, the direct evidence of TRIM22 on monocyte apoptosis remains absent. Methods TRIM22 was constructed and transfected into a monocytic cell line THP-1 cell. Apoptosis of transfected cells was induced by STS and tested by flow cytometry. The caspase pathways involved in TRIM22-related apoptosis were illustrated by inhibitory experiments. Proapoptotic/antiapoptotic protein were measured by immunoblot. Results Overexpression of TRIM22 in THP-1 cells caused extensive apoptosis induced by STS; The activation of caspase-9 and caspase-3, and the release of cytochrome c were increased in TRIM22-overexpressing cells; Inhibition of caspase activation protected the cells from apoptosis augmented by TRIM22; Bak was upregulated in TRIM22 overexpressing monocytes. Conclusions Overexpression of TRIM22 in human acute monocytic leukemia cell THP-1 caused extensive apoptosis induced by STS both in absence and presence of lipopolysaccharide, which was associated with elevated cleavage of caspase-9 and caspase-3, and release of cytochrome c. Z-VAD-fmk, a pan caspase inhibitor, prevented TRIM22-induced apoptosis. Western blot found that Bak was upregulated in TRIM22 overexpressing monocytes.