Induction of cell cornification and enhanced squamous-cell marker SPRR1 gene expression by phorbol ester are regulated by different signaling pathways in human conducting airway epithelial cells

Phorbol ester is a strong inducer for both cell cornification and squamous-cell marker SPRR1 gene expression in conducting airway epithelial cells. However, the signaling pathways involved in the regulation of both events have not been completely elucidated. The current study focuses on the common and divergent pathways involved in the induction of these two activities by phorbol-13-myristate-12-acetate (PMA). Using a protein kinase (PK) C inhibitor, bisindolylmaleimide I, PMA-induced cell cornification and SPRR1 gene expression were abolished. Further, a PKC activator, indolactam V, induced cell cornification in the absence of PMA treatment. These results suggest a PKC-dependent signaling pathway for both gene induction and enhanced cell cornification by PMA. However, a mitogen-activated protein kinase-specific inhibitor, PD98059, could only block the gene induction event but failed to prevent cell cornification induced by PMA. These results suggest that diverse signaling pathways after PKC activation by PMA are involved in the regulation of these two events.