Differentiation of monocytoid THP-1 cells with phorbol ester induces expression of prostaglandin endoperoxide synthase-1 (COX-1).

Prostaglandin endoperoxide synthase (PGH synthase) is responsible for converting arachidonic acid to PGH2, the common precursor of prostaglandins. It has been shown previously that phorbol ester-induced differentiation of the THP-1 human monocytic leukemia cell line is accompanied by induction of PGH synthase enzyme and enhanced capacity to produce prostaglandins. However, the identity of the isoform of PGH synthase that is induced under these conditions has not been established. Northern and Western analyses revealed a dramatic increase in levels of PGH synthase-1 mRNA and protein levels within 24 hr after treatment of THP-1 cells with phorbol ester. No significant increase in PGH synthase-2 mRNA or protein was observed. The increases in PGH synthase-1 were accompanied by enhanced capacity of the cells to produce PGE2. These findings indicate that expression of PGH synthase-1 is greatly enhanced in THP-1 cells by treatment with an agent that induces differentiation.