INHIBITION OF NUCLEAR FACTOR KAPPA-B BY PROSTAGLANDIN A(1) - AN EFFECT ASSOCIATED WITH HEAT-SHOCK TRANSCRIPTION FACTOR ACTIVATION

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 ch aracterized by antiviral activity against several viruses, including h uman immunodeficiency virus type 1 (HIV-1), and by the ability to indu ce heat shock protein expression through activation of the heat shock transcription factor. Here we report that PGA(1) 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-ch loramphenicol acetyltransferase transient transfection experiments. PG A(1) acts by inhibiting phosphorylation and preventing degradation of the NF-kappa B inhibitor I kappa B-alpha. Inhibition does not require protein synthesis, is dependent on the presence of a reactive cyclo-pe ntenonic moiety, and is associated with heat shock transcription facto r activation. Because NF-kappa B is critically involved in the activat ion of immunoregulatory and viral genes, inhibition of its activity co uld be a major component of the immunosuppressive and antiviral activi ty of PGs.