A mechanism of transcriptional regulation of the CSF-1 gene by interferon-gamma.

Interferon (IFN)-gamma exerts multiple functions including antiviral, anti-proliferative and immunomodulatory activities, which are mediated through the JAK-STAT pathway. We observed that IFN-gamma significantly increases the production of colony stimulating factor-1 (CSF-1) by a human lung carcinoma cell line, A549. To gain insight into this mechanism, we determined the unknown nucleotide sequences of 5'-flanking region of human CSF-1 gene. About 60 bases upstream of the transcription start site of the CSF-1 gene contains a possible gamma interferon activated site (GAS), TTCCCATAA. The promoter assay and the electrophoretic mobility gel shift assay revealed that IFN-gamma stimulates transcription of the CSF-1 gene through this sequence, which binds STAT1.