REGULATION OF 2 ISOZYMES OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE AND THROMBOXANE SYNTHASE IN HUMAN MONOBLASTOID CELL-LINE U937

The mechanism responsible for the rapid increase of thromboxane A(2) s ynthesis by cells of the human monoblastoid cell line U937, which were differentiated with 12-O-tetradecanoyl-phorbol-13-acetate, induced by lipopolysaccharide (LPS) was studied. Both RNA blot and immunoblot an alyses showed that LPS increased the levels of prostaglandin endoperox ide synthase-l (PES-I) and -2 (PES-2) in a time-dependent manner, and the modes of induction of the two isozymes differed. The maximum PES-1 mRNA level was 1.6 times higher 36 h after than before stimulation by LPS, and that of PES-P mRNA was elevated about 20-fold at its peak at 12 h after stimulation. Consequently, the immunoreactive PES-I and PE S-L? protein levels also increased time-dependently after LPS stimulat ion. However, the effects of LPS on the thromboxane synthase mRNA and protein levels were much less marked. These results indicate that LPS- induced thromboxane synthesis by the differentiated cells was regulate d at the levels of the two PES isozymes, predominantly at the PES-2 le vel.