T. Nanayama et al., REGULATION OF 2 ISOZYMES OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE AND THROMBOXANE SYNTHASE IN HUMAN MONOBLASTOID CELL-LINE U937, Prostaglandins, 49(6), 1995, pp. 371-382
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.