Phorbol myristate acetate-differentiated THP-1 cells display increased levels of MHC class I and class II mRNA and interferon-gamma-inducible tumoricidal activity.
The protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and mezerein induce differentiation of human monocytic leukemia (THP-1) 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-1 cells secrete interleukin-1 beta as well as a tumor cell growth inhibitory factor whose basal level is increased in response to interferon-gamma. However, tumoricidal, as opposed to tumoristatic, activity of differentiated THP-1 has not been documented. We report herein that PMA-differentiated THP-1 cells (PD/THP-1) 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-gamma. These two characteristics are important components of the macrophage phenotype. The results presented in this study extend previous observations on THP-1 cells by demonstrating that PD/THP-1 cells display a critical, immunologically relevant macrophage function, and therefore, enhance the utility of THP-1 as a model for the in vitro study of immunomodulatory drugs and macrophage-mediated cytocidal processes.
Howard University Cancer Center, Washington, DC 20060.
A
A
Asseffa
L A
LA
Dickson
S
S
Mohla
T A
TA
Bremner
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate