Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells

Vanadate and peroxovanadium derivatives are potent inhibitors of protein ty rosine phosphatases (PTPs) and exhibit insulinomimetic activities in severa l cell systems. We have found that in 293 and 293T cells, intercellular adh esion molecule-1 (ICAM-1) gene transcription is activated by bpV(Pic), a pi colinic acid-stabilized peroxovanadium derivative. To identify the bpV(Pic) -responsive element(s), several deletion and site-specific mutants of the I CAM-1 gene promoter cloned upstream from the firefly luciferase reporter ge ne were transiently transfected into both cell lines. Deletion or site-spec ific mutation of the NF-kappaB site did not affect bpV(Pic) responsiveness, whereas deletion or mutation of the palindromic interferon-gamma -responsi ve element (pI gamma RE)/gamma -interferon activated sequence site greatly decreased bpV(Pic) responsiveness in both cell types. bpV(Pic) synergistica lly co-operated with interferon-gamma to increase the transcriptional activ ity of the ICAM-1 promoter. Electrophoretic mobility-shift assays showed th at bpV(Pic) induces signal transducers and activators of transcription (STA T)-1 binding to the ICAM-1 pI gamma RE/GAS in 293T cells, suggesting that t he peroxovanadium compound specifically inhibits the phosphatase(s) require d to regulate the JAK/STAT signal-transduction pathway.