| First Author | Higuchi T | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 318 |
| Issue | 1 | Pages | 46-52 |
| PubMed ID | 15110751 | Mgi Jnum | J:89393 |
| Mgi Id | MGI:3040022 | Doi | 10.1016/j.bbrc.2004.04.002 |
| Citation | Higuchi T, et al. (2004) Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB. Biochem Biophys Res Commun 318(1):46-52 |
| abstractText | We report here that the transcriptional activity of NF-kappaB is negatively regulated by protein disulfide isomerase (PDI). Over-expression of PDI in RAW 264.7 cells strongly suppressed the LPS-induced production of inflammatory cytokines as well as NF-kappaB-dependent luciferase activity. This negative regulation of NF-kappaB was reversed by bacitracin, a PDI inhibitor. Interestingly, NF-kappaB/DNA complex formation and phosphorylation of NF-kappaB subunits was intact in PDI-expressing cells following stimulation with LPS. In addition, PDI and another redox regulator, thioredoxin (TRX), had opposite effects on NF-kappaB-dependent gene expression: activation of the NF-kappaB pathway by TRX was suppressed by expression of PDI in a dose-dependent manner. Finally, PDI expression was induced by the anti-inflammatory cytokine IL-10, and IL-10-mediated inhibition of LPS-induced IL-6 expression was reduced by bacitracin. These findings clearly demonstrate that PDI is a negative regulator of NF-kappaB, and may act downstream of IL-10 in this signaling pathway. |
