Our previous study has demonstrated the potentiation by uridine triphosphate (UTP) of nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated murine J774 macrophages. In this study, we found that the amount of interleukin-6 (IL-6) release in response to LPS stimulation was greatly enhanced in the presence of UTP. This enhancement exhibited concentration dependence and occurred after 8 h of treatment with LPS. RT-PCR analysis indicated that the steady-state level of IL-6 mRNA induced by LPS was apparently increased upon co-addition of UTP. The potentiation by UTP was inhibited by the treatment with U73122 (a phosphatidylinositol-phospholipase C inhibitor), BAPTA/AM (an intracellular Ca2+ chelator), KN-93 (a selective inhibitor of calmodulin-dependent protein kinase) or PDTC (a nuclear factor κB inhibitor). To understand the cross-regulation among NO, PGE2 and IL-6, all of which are dramatically induced after LPS stimulation, the effects of L-NAME (a nitric oxide synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), NS-398 (a cycloxygenase-2 inhibitor) and IL-6 antibody were tested. The results revealed the positive regulation between PGE2 and IL-6 synthesis because NS- 398 and indomethacin inhibited LPS plus UTP-induced IL-6 release, and IL-6 antibody attenuated LPS plus UTP-induced PGE2 release. Taken together these results reinforce the role of UTP as a regulatory element in inflamed sites by demonstrating the capacity of this nucleotide to potentiate LPS-induced release of inflammatory mediators.
|頁（從 - 到）||425-432|
|期刊||Journal of Biomedical Science|
|出版狀態||已發佈 - 十一月 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Chen, B. C., & Lin, W. W. (1999). Potentiation of lipopolysaccharide-induced IL-6 release by uridine triphosphate in macrophages: Cross-interaction with cyclooxygenase-2- dependent prostaglandin E2 production. Journal of Biomedical Science, 6(6), 425-432. http://download.springer.com/static/pdf/89/art%253A10.1007%252FBF02253674.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2FBF02253674&token2=exp=1470214258~acl=%2Fstatic%2Fpdf%2F89%2Fart%25253A10.1007%25252FBF02253674.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252FBF02253674*~hmac=c0329d4a129e79c14a7994684c0b164ffc68e2e7a10bca6a001b7e7c6b745f15