Purchase this article with an account.
A.P. Ghafoori, S. Masli, J.W. Streilein; TGFß Treatment of ACAID-Inducing Antigen Presenting Cells Prevents IL-12 Secretion by Increasing Nuclear Expression of the NFB Inhibitor IB . Invest. Ophthalmol. Vis. Sci. 2003;44(13):750.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The NFΚB transcription factor family is a key regulator of several pro-inflammatory cytokines, including IL-12. APCs treated with TGFß are able to induce ACAID in part because they fail to express IL-12. We wished to determine if treatment of APCs with TGFß would alter the nuclear expression of IΚBα, the endogenous inhibitor of NFΚB. Methods: APCs were treated separately with TGFß and IFNγ/LPS for 1, 2, 4 and 18 hours. Nuclear and cytoplasmic extracts were obtained and analyzed with western blot analysis for expression of IΚBα and of the NFΚB subunits p65 and c-Rel. Results: Compared to the untreated APCs and APCs treated with a typical inflammatory stimulus (IFNγ/LPS), TGFß-treated APCs displayed early and sustained increased nuclear, but not cytoplasmic, expression of IΚBα, detected at 1 through 18 hours. Additionally, while INFγ/LPS treatment induced translocation of p65 and c-Rel into the nucleus, TGFß had no such effect. Conclusions: Within 1 hour TGFß treatment of APCs induces high levels of nuclear IΚBα expression. Unlike IΚBß, IΚBα is able to enter the nucleus and inhibit NFΚB activity by exporting NFΚB dimers out of the nucleus. Since NFΚB is required for expression of IL-12, and since IL-12 inhibits ACAID induction, we propose that TGFß confers ACAID-inducing properties on APCs by globally inhibiting the pro-inflammatory transcription factor NFΚB.
This PDF is available to Subscribers Only