Phorbol-12-myristate-13-acetate (PMA) mediated transcriptional regulation of Oncostatin-M

- PMA induces transcriptional upregulation of Oncostatin-M in U937 cells.
- A proximal region (CCAAT) of osm promoter is the PMA-responsive element.
- PMA promotes increased expression of C/EBP-β and subsequent binding to CCAAT.
- C/EBP-β inhibition results in consequent expression of CHOP and mutual association.
- C/EBP-β knockdown and inhibition cause abrogated transcription through CCAAT box.

Oncostatin-M (OSM), an IL-6 family cytokine, exhibits varied roles in different patho-physiological conditions. Differential expression of OSM in response to varying stimuli indicates importance of its regulation of expression. The present study illustrated transcriptional induction of osm on treatment with chemical inducer, phorbol-12-myristate-13-acetate (PMA). Following initial hours of PMA treatment, a nuclear protein C/EBP-β binds specifically to the CCAAT consensus sequence at the proximal end of the OSM promoter. Genistein (a specific Tyr phosphorylation inhibitor) leads to the interaction of CHOP (C/EBP Homologous Protein) with C/EBP-β, thus negatively regulating it. Knockdown of C/EBP-β also leads to inhibition of PMA-mediated OSM induction.