Journal of Biomedical Science

, Volume 6, Issue 6, pp 425–432 | Cite as

Potentiation of lipopolysaccharide-induced IL-6 release by uridine triphosphate in macrophages: Cross-interaction with cyclooxygenase-2-dependent prostaglandin E2 production

  • B. C. Chen
  • W. W. Lin
Original Paper

Abstract

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.

Key Words

Cyclooxygenase Interleukin-6 Macrophage Nitric oxide Prostaglandin E2 Pyrimidinoceptor 

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Copyright information

© National Science Council 1999

Authors and Affiliations

  • B. C. Chen
    • 1
  • W. W. Lin
    • 1
  1. 1.Department of Pharmacology College of MedicineNational Taiwan UniversityTaipeiTaiwan

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