Differential effects of triptolide and tetrandrine on activation of COX-2, NF-kappaB, and AP-1 and virus production in dengue virus-infected human lung cells.

Abstract

Most virus infections induce cycloxygenase-2 (COX-2) expression and subsequent prostaglandin E(2) (PGE(2)) production in cells, an inflammatory response that might be detrimental to virus replication and pathogenesis. This response in dengue virus infection remains to be elucidated. Triptolide and tetrandrine, compounds derived from two commonly used Chinese herbs, both demonstrate anti-inflammatory and immunosuppressive effects partly through modulation of COX-2 expression and, hence, may have antiviral effects. In this study, we examined, firstly, the immune response to dengue virus infection with respect to COX-2 expression and PGE(2) production in human lung cells (A549), liver cells (HepG2) and dendritic cells. Secondly, we assessed the potential antiviral effects of triptolide and tetrandrine on dengue virus infection vis-à-vis expression of COX-2, PGE(2), transcription factors, as well as virus production. We found that dengue virus infection enhanced COX-2 expression and PGE(2) production in A549 cells, similarly to the response in dendritic cells, but not in HepG2 cells. In dengue virus-infected A549 cells, nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) were also activated, and both were dose-dependently inhibited by triptolide (0.5-4 ng/ml). Tetrandrine (1-10 microM) had no similar immunosuppressive effects and, moreover, at higher concentrations, enhanced NF-kappaB and AP-1 activity, COX-2 expression and PGE(2) production. However, unexpectedly, tetrandrine, but not triptolide, dose-dependently suppressed dengue virus production in A549 cells, independent of PGE(2) level. Our findings imply that triptolide and tetrandrine may attenuate dengue virus infection in human lung cells, but through distinct pathways.

• Authors: Jun-Ting Liou, Zih-Yan Chen, Ling-Jun Ho, Shih-Ping Yang, Deh-Ming Chang, Chun-Chin Liang, Jenn-Haung Lai
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 589 Issue 1-3 Pg. 288-98 (Jul 28 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18565510 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antiviral Agents
• Benzylisoquinolines
• Diterpenes
• Epoxy Compounds
• Immunologic Factors
• NF-kappa B
• Phenanthrenes
• Transcription Factor AP-1
• triptolide
• tetrandrine
• Cyclooxygenase 2
• PTGS2 protein, human
• Dinoprostone

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antiviral Agents (pharmacology)
• Benzylisoquinolines (pharmacology)
• Cell Line, Tumor
• Cyclooxygenase 2 (metabolism)
• Dendritic Cells (drug effects, enzymology, virology)
• Dengue Virus (growth & development, pathogenicity)
• Dinoprostone (metabolism)
• Diterpenes (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Epoxy Compounds (pharmacology)
• Humans
• Immunologic Factors (pharmacology)
• Liver (drug effects, enzymology, virology)
• Lung (drug effects, enzymology, pathology, virology)
• NF-kappa B (metabolism)
• Phenanthrenes (pharmacology)
• Time Factors
• Transcription Factor AP-1 (metabolism)
• Virus Replication (drug effects)