Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions.
To examine the potential contribution of endothelial cell cNOS (ec-cNOS) and inducible NOS (iNOS) in controlling vascular tone under normal versus inflammatory conditions, we performed Northern hybridizations to examine the differential expression of each NOS mRNA in human aortic endothelial cells (AOEC) and human aortic smooth muscle cells (AOSMC) cultured for 8 h in the presence or absence of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) and LPS. Cytokine/LPS treatment induced a 4.4 kb iNOS mRNA in the human AOSMC; in contrast, cytokine/LPS treatment down regulated the expression of ec-cNOS mRNA in the AOEC. No iNOS mRNA was detected in the AOEC under the conditions examined. These results suggest that under specific inflammatory conditions the generation of NO in vascular tissue switches from ec-cNOS in the endothelium to iNOS in the smooth muscle.
MacNaul
K L
KL
Merck Research Laboratories, Rahway, NJ 07065.
Hutchinson
N I
NI
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology* / Q000503:physiopathology; D015152:Blotting, Northern; D002478:Cells, Cultured; D015342:DNA Probes; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000503:physiopathology; D019001:Nitric Oxide Synthase; D011061:Poly A / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D012016:Reference Values; D015183:Restriction Mapping
D015342:DNA Probes; D007527:Isoenzymes; D012333:RNA, Messenger; D011061:Poly A; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases