期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1997
卷号:94
期号:2
页码:746-750
DOI:10.1073/pnas.94.2.746
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Prostaglandins (PGs) function as intracellular signal mediators in the regulation of a variety of physiological and pathological processes, including inflammation and immune responses. Cyclopentenone PGs are characterized by antiviral activity against several viruses, including human immunodeficiency virus type 1 (HIV-1), and by the ability to induce heat shock protein expression through activation of the heat shock transcription factor. Here we report that PGA1 is a potent inhibitor of nuclear factor-{kappa}B (NF-{kappa}B) activation in human cells and of NF-{kappa}B-dependent HIV-1 transcription in long terminal repeat-chloramphenicol acetyltransferase transient transfection experiments. PGA1 acts by inhibiting phosphorylation and preventing degradation of the NF-{kappa}B inhibitor I{kappa}B-. Inhibition does not require protein synthesis, is dependent on the presence of a reactive cyclopentenonic moiety, and is associated with heat shock transcription factor activation. Because NF-{kappa}B is critically involved in the activation of immunoregulatory and viral genes, inhibition of its activity could be a major component of the immunosuppressive and antiviral activity of PGs.
关键词:antiviral ; HIV ; IκB-α ; tumor necrosis factor α