- 作者: B.C. Chen W.W. Lin
- 作者服務機構: Department of Pharmacology, College of Medicine, National taiwan University,Taipei, Taiwan,
- 中文摘要: --
- 英文摘要: Our previous study has demonstrated the potentiationby uridine triphosphate (UTP) of nitric oxide (NO) andprostaglandin E (PGE ) production in lipopolysaccha-ride (LPS)-stimulated murine J774 macrophages. In thisstudy, we found that the amount of interleukin-6 (IL-6)release in response to LPS stimulation was greatly en-hanced in the presence of UTP. This enhancement exhib-ited concentration dependence and occurred after 8 h oftreatment with LPS. RT-PCR analysis indicated that thesteady-state level of IL-6 mRNA induced by LIPS wasapparently increased upon co-addition of UTP. The po-tentiation by UTP was inhibited by the treatment withU73122 (a phosphatidylinositol-phospholipase C inhibi-for), BAPTA/AM (an intracellular Ca chelator), KN-93 (aselective inhibitor of calmodulin-dependent protein ki-nase) or PDTC (a nuclear factor KB inhibitor). To under-stand the cross-regulation among NO, PGE and IL-6, allof which are dramatically induced after LPS stimulation,the effects of L-NAME (a nitric oxide synthase inhibitor),indomethacin (a cyclooxygenase inhibitor), NS-398 (acycloxygenase-2 inhibitor) and IL-6 antibody weretested. The results revealed the positive regulation be-tween PGE and IL-6 synthesis because NS-398 and indo-methacin inhibited LPS plus UTP-induced IL-6 release,and IL-6 antibody attenuated LPS plus UTP-inducedPGE release. Taken together these results reinforce therole of UTP as a regulatory element in inflamed sites bydemonstrating the capacity of this nucleotide to poten-tiate LPS-induced release of inflammatory mediators.
- 中文關鍵字: --
- 英文關鍵字: Cyclooxygenase. Interleukin-6. Macrophage. Nitric oxide. prostaglandin E2. Pyrimidinoceptor