Open AccessInhibition of nuclear factor κB by prostaglandin A1: An effect associated with heat shock transcription factor activation
Author(s) -
Antônio Rossi,
Giuliano Elia,
M. Gabriella Santoro
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.2.746
Subject(s) - heat shock factor , transcription factor , biology , heat shock , heat shock protein , chloramphenicol acetyltransferase , nf κb , iκbα , microbiology and biotechnology , nfkb1 , transfection , transcription (linguistics) , hsp70 , signal transduction , gene expression , biochemistry , promoter , gene , linguistics , philosophy
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-κB (NF-κB) activation in human cells and of NF-κB-dependent HIV-1 transcription in long terminal repeat-chloramphenicol acetyltransferase transient transfection experiments. PGA1 acts by inhibiting phosphorylation and preventing degradation of the NF-κB inhibitor IκB-α. 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-κB 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.