Role of interferon regulatory factor 1 in monocyte/macrophage differentiation

Abstract

Interferon regulatory factor‐1 (IRF‐1) has been recognized as an important tumor suppressor and growth regulatory transcription factor, which is also involved in cell differentiation. In this study we investigated the role of IRF‐1 in phorbol 12‐myristate 13‐acetate (PMA)‐induced monocyte/macrophage differentiation of human monoblastic U937 cells. For this purpose U937 cells were stably transfected with a vector overexpressing IRF‐1 antisense mRNA (U937 IRF‐1A cells) and with the SV‐40 empty vector (U937‐SV40 e.v. cells). We report here that U937 and U937‐SV40 e.v. cells differentiated into macrophage‐like cells upon PMA stimulation and showed IRF‐1 up‐regulation. On the contrary, U937 IRF‐1A cells stimulated with PMA kept an undifferentiated phenotype and proliferated actively. A direct correlation between induction of IRF‐1 and up‐regulation of IRF‐1 gene targets such as ornithine decarboxylase (ODC) and WAF‐1/CIP‐1 was also observed in U937 cells. On the other hand U937 IRF‐1A cells down‐regulated ODC and did not express WAF‐1. Results show that IRF‐1 plays a pivotal role in PMA‐induced monocyte/macrophage differentiation.