Transcribing the Cross-Talk of Cytokine-Induced Tetrahydrobiopterin Synthesis in Endothelial Cells

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Abstract
(iNOS) gene expression has been observed in the presence of inflammatory cytokines, suggesting that basal levels of GT- PCH I and BH4 are not adequate for optimal iNOS function. Individual cytokines such as tumor necrosis factor- (TNF- ), interferon- (INF-), or interleukin-1 (IL-1) have been shown to induce little GTPCH I mRNA or protein expression. However, the combination of these cytokines have been shown to induce a robust activation of GTPCH I mRNA, protein, and BH4 production both in vivo and in vitro. It is important to note that these observations were made on vascular smooth muscle cells whereas in endothelium, induc- tion of GTPCH I was not associated with induction of iNOS.14,16 Whether high production of BH4 in endothelium activated by cytokines is designed to provide additional support for iNOS enzymatic activity in smooth muscle cells or it has some other functions remains to be determined. In this issue of Circulation Research, Huang and col-