Up‐regulation of human iNOS transcription by coactivator p300

Served as one of general transcription coactivators, p300 plays an important role in mediating gene transcriptional activation. Our previous work demonstrated that human iNOS expression can be highly induced with the cytokine mixture (CM) of TNFα + IL‐1β + IFNγ. In this study, we explored the potential function of p300 in the regulation of human iNOS gene expression. Our initial results showed that overexpression of p300 by transient transfection in human A549 lung cells significantly increased the basal and cytokine induced human iNOS promoter activities. Interestingly, p300 activated cytokine induced human iNOS transcription which was completely abrogated by the deletion of an enhancer region between ‐5 kb and ‐6 kb in the hiNOS upstream promoter. However, the enhanced basal promoter activity by p300 overexpression still remained high even with the enhancer deletion. Our data suggest that coactivator p300 is capable of up‐regulating human iNOS transcription. The transcription machinery responsible for p300 interaction with necessary transcription factors is being further investigated.