| First Author | Panchanathan R | Year | 2013 |
| Journal | Mol Immunol | Volume | 53 |
| Issue | 1-2 | Pages | 15-23 |
| PubMed ID | 22784990 | Mgi Jnum | J:188158 |
| Mgi Id | MGI:5439246 | Doi | 10.1016/j.molimm.2012.06.013 |
| Citation | Panchanathan R, et al. (2013) Murine BAFF expression is up-regulated by estrogen and interferons: Implications for sex bias in the development of autoimmunity. Mol Immunol 53(1-2):15-23 |
| abstractText | 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-alpha) 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-alpha or gamma) 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-alpha, IRF5, or STAT1 expression in splenic cells decreased expression of BAFF. Moreover, treatment of RAW264.7 macrophage cells with IFN-alpha, IFN-gamma, 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. |
