Type II NOS and COX-2 are expressed after stimulation with proinflammatory cytokines in a variety of tissues including smooth muscle cells (SMC). It is still unclear whether: a) cytokine-mediated inflammation is attributed to the induction of type II NOS and/or COX-2, and b) the vascular actions of cytokines in inflammatory diseases are species and tissuedependent. In the present study we have tested the hypothesis that E. coli LPS, IL-1β, and TNFα selectively induce type II NOS or COX-2 in different human and animal vascular SMC. Type II NOS and COX-2 activity were assessed by cGMP and cAMP accumulation, respectively, over a 15 min period in the presence of phosphodiesterase inhibition. Passage six cultured human renal artery and pulmonary vein SMC incubated 5 hrs with LPS, IL-1β or TNF α did not express type II NOS activity. On the other hand, LPS and IL-1β caused a 150- to 156-fold increase in cGMP levels in passage three cultured rat aortic SMC. In contrast, human pulmonary vein SMC exposed to LPS, IL-1β, or TNFα expressed a significant level of COX-2 activity as indicated by a 2-5 fold increase in cAMP accumulation, whereas in rat aortic SMC, COX-2 was not expressed following treatment with these agents. These results suggest that the induction of type II NOS and COX-2 by cytokines in vascular smooth muscle is both species and cell type dependent. (Supported by HL-52958 and American Heart Assoc. Ga. Affiliate).
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology