- Paper Report
- Open Access
Cytokine dysregulation in macrophages of lupus-prone mice
- Sylvie Fournel1
© Biomed Central Ltd 2001
- Published: 12 January 2001
In systemic lupus erythematosus (SLE), various autoantibodies recognize antigens that are modified and relocalized during apoptosis, suggesting that apoptotic cells may play a role in breakdown of tolerance and disease development. However, very little is known about intracellular signaling events induced by uptake of apoptotic cells. The authors have already reported that peritoneal and bone-marrow-derived macrophages from prediseased MRL/++ and MRL/lpr SLE-prone mice display a defect in lipopolysaccharide (LPS)-induced expression of several cytokines when compared with peritoneal macrophages derived from BALB/c mice. Therefore they investigated if these defects are present in other lupus-prone murine strains, and if apoptotic cells participate in these defects.
The defect in LPS-induced cytokine mRNA production was dependent on the presence of fetal bovine serum (FBS) and was not detectable if the MRL/++ mice peritoneal macrophages were cultured in FBS-free medium or in a medium complemented with delipidated FBS. This defect was found in 10 different lupus-prone strains. It was not observed in any of the 13 nonautoimmune strains tested. In the presence of FBS-treated apoptotic thymocytes, LPS treatment increased interleukin (IL)-1 mRNA production by macrophages derived from the BALB/c strain and, to a lesser extent, the MLR/++ strain. The defect in IL-1 mRNA production was not observed in the presence of FBS-treated viable thymocytes, suggesting that FBS-induced modifications of apoptotic cells were responsible for the defect. The authors conclude that FBS or apoptotic cells can reduce IL-1 expression in macrophages, and that this defect is a characteristic of lupus-prone mice.
Lupus-prone mice, northern blotting, RNAse protection assays