Transcriptional activation of the heme oxygenase gene by TPA in mouse M1 cells during their differentiation to macrophage.

The activation of the heme oxygenase (HO), fos, and AP-1 genes was determined at intervals after treatment of M1 cells (derived from mouse myeloleukemia) with heme or 12-O-tetradecanoylphorbol 13-acetate (TPA). On treatment with heme, M1 cells did not differentiate into macrophage but their HO gene was activated and showed maximum transcriptional activity after treatment with heme for 2 h. In contrast, on treatment with TPA, these cells adhered to the culture flasks within 5 h and differentiated into macrophage-like cells. Moreover, the sequential activation of the fos, AP-1, and HO genes was observed during this period, with the maximal transcriptional activities after TPA treatment for 0.5, 1, and 1.5 h, respectively. Thus, the HO gene was activated by treatment with either heme or TPA, and the latter activation was associated with activations of the fos and AP-1 genes. As the rat HO gene is known to have a TPA-sensitive element in its promoter region, this gene was suggested to be activated by a fos-AP-1 complex protein.