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Murine BAFF expression is up-regulated by estrogen and interferons: implications for sex bias in the development of autoimmunity.

Abstract：

:Systemic lupus erythematosus (SLE) in patients and certain mouse models exhibits a strong sex bias. Additionally, in most patients, increased serum levels of type I interferon (IFN-α) are associated with severity of the disease. Because increased levels of B cell activating factor (BAFF) in SLE patients and mouse models are associated with the development of SLE, we investigated whether the female sex hormone estrogen (E2) and/or IFNs (IFN-α or γ) could regulate the expression of murine BAFF. We found that steady-state levels of BAFF mRNA and protein were measurably higher in immune cells (CD11b(+), CD11c(+), and CD19(+)) isolated from C57BL/6 females than the age-matched male mice. Treatment of immune cells with IFN or E2 significantly increased levels of BAFF mRNA and protein and a deficiency of estrogen receptor-α, IRF5, or STAT1 expression in splenic cells decreased expression of BAFF. Moreover, treatment of RAW264.7 macrophage cells with IFN-α, IFN-γ, or E2 induced expression of BAFF. Interestingly, increased expression of p202, an IFN and estrogen-inducible protein, in RAW264.7 cells significantly increased the expression levels of BAFF and also stimulated the activity of the BAFF-luc-reporter. Accordingly, the increased expression of the p202 protein in lupus-prone B6.Nba2-ABC than non lupus-prone C57BL/6 and B6.Nba2-C female mice was associated with increased expression levels of BAFF. Together, our observations demonstrated that estrogen and IFN-induced increased levels of the p202 protein in immune cells contribute to sex bias in part through up-regulation of BAFF expression.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Panchanathan R,Choubey D

doi

10.1016/j.molimm.2012.06.013

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

15-23

issue

1-2

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(12)00335-5

journal_volume

53

pub_type

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