Phorbol myristate acetate-differentiated THP-l cells display increased levels of MHC class I and class II mRNA and interferon-γ-inducible tumoricidal activity

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The protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and mezerein induce differentiation of human monocytic leukemia (THP-l) cells along the monocyte/macrophage pathway of development. The differentiated cells express many important macrophage functions including phagocytosis and the secretion of immunomodulatory cytokines. Mezerein-differentiated THP-l cells secrete interleukin-lβ as well as a tumor cell growth inhibitory factor whose basal level is increased in response to interferon-γ. However, tumoricidal, as opposed to tumoristatic, activity of differentiated THP-l has not been documented. We report herein that PMA-differentiated THP-l cells (PD/THP-l) contain elevated levels of MHC class I and class II mRNAs even in the absence of activating factors, and kill HT-29 human colon carcinoma cells when stimulated with recombinant human interferon-γ. These two characteristics are important components of the macrophage phenotype. The results presented in this study extend previous observations on THP-l cells by demonstrating that PD/THP-l cells display a critical, immunologically relevant macrophage function, and therefore, enhance the utility of THP-l as a model for the in vitro study of immunomodulatory drugs and macrophage-mediated cytocidal processes. © 1993.

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