Induction of human prostaglandin endoperoxide H synthase-2 (PHS-2) mRNA by TCDD

Abstract

Numerous transcription response elements (e.g. AP-1, AP-2, GRE, CREB, as well as DRE) have been identified in the transcription regulation region of the PHS-2 gene in both mouse and human. The discovery of a DRE in the region raised the possibility that PHS-2 could be induced by TCDD, a dioxin compound. The time course and dose dependence of TCDD induction of PHS-2 mRNA expression were observed in HUVEC, primary human epithelial cells. In the observed time range (0–24 hours) the steady-state mRNA expression levels of PHS-2, as well as of mRNA for CYPlA1, increased with time at a TCDD dose of 20 nM. At the 24 hour time point, TCDD-treated cells displayed significant dose-dependent elevation of PHS-2 over the range of 0–40 nM TCDD. The increases in PHS-2 mRNA in both the time course and dose dependence experiments were consistent with that of CYPIAI. In contrast, mRNA for PHS-1, the constitutively expressed isoform of PHS, did not show significant changes under the conditions tested. These results are the first to indicate that TCDD can elevate PHS-2 mRNA level in a time and dose dependent manner. Further work needs to be done to learn the molecular mechanism of activation of PHS-2 by TCDD and the relation of TCDD action with other regulatory factors in the control of PHS-2 expression.