New insights into the role and mechanism of macrophage migration inhibitory factor in steroid-resistant patients with systemic lupus erythematosus Full Text
Arthritis Research & Therapy, 05/03/2012
Wang FF et al. – The results indicated that migration inhibitory factor (MIF) may play a role in the formation of steroid–resistance in systemic lupus erythematosus (SLE) by affecting the NF–kappaB/IkappaB signaling cascade. As a regulator of glucocorticoid sensitivity, MIF may be a potential target for steroid sparing.
Methods- 62 patients with SLE (40 steroid–sensitive and 22 steroid–resistant) and 21 normal controls were recruited.
- Serum levels of MIF were measured by enzyme–linked immunosorbent assay (ELISA).
- Cytosolic MIF and IkappaB expression in peripheral blood mononuclear cells (PBMC) were determined by Western blotting.
- The electrophoretic mobility shift assay was assessed by NF–kappaB in nuclear aliquots. Gene silencing was applied to reduce expression of MIF in PBMCs in steroid–resistant patients.
- PBMCs obtained from steroid–sensitive patients were treated with recombinant human MIF of different concentrations.
- MIF levels in serum and PBMCs were higher in steroid–resistant patients compared to steroid–sensitive patients and controls.
- In contrast to the steroid–sensitive group, NF–kappaB levels were significantly higher and IkappaB levels lower in steroid–resistant patients.
- After MIF gene silencing, IkappaB levels in cells from steroid–resistant patients were increased.
- In steroid–sensitive patients, a decrease in IkappaB levels and an increase in NF–kappaB expression from baseline were detected in PBMCs treated with a higher concentration of rMIF.
- rMIF did not regulate expression of IkappaB and NF–kappaB in PBMCs from patients treated with an anti–MIF monoclonal antibody.
