Dysregulated neurotrophin mRNA production by immune cells of patients with relapsing remitting multiple sclerosis.

Abstract

Recent studies have suggested a neuroprotective activity of the lesion-infiltrating immune cells in multiple sclerosis (MS) by secretion of neurotrophins. We had earlier reported that immune cells from relapsing remitting MS (RR-MS) patients secrete low levels of brain-derived neurotrophic factor (BDNF), and that its secretion is dysregulated after CD40 stimulation. Here, we measured mRNA levels for BDNF, NT3 and NGF-beta mRNA in unstimulated PBMCs and found levels lower in untreated RR-MS patients than in healthy controls (HC). T-cell stimulation with anti-CD3/CD28 mAb up-regulated neurotrophin mRNA expression in untreated RR-MS patients and not in HC, whereas stimulation of PBMCs with anti-CD40 mAb up-regulated neurotrophin mRNA expression in HC and not in RR-MS patients. Further cellular analyses of the production of the neurotrophin mRNA in individual cells revealed that T cells were the main producers of the neurotrophin mRNA in RR-MS patients, and that monocytes were the main producers of NT3 and NGF-beta mRNA in HC. BDNF mRNA was similarly produced in monocytes and T cells in the HC group. The cytokines TNF-alpha and IL-17 up-regulated the expression of neurotrophin mRNA in HC but not in RR-MS patients. The neuroprotective activity of PBMCs appeared to be dysregulated in untreated patients with RR-MS, while the differences between the IFN-beta-treated RR-MS patients and the HC were smaller.

DOI: 10.1016/j.jns.2010.05.019

Cite this paper

@article{Urshansky2010DysregulatedNM, title={Dysregulated neurotrophin mRNA production by immune cells of patients with relapsing remitting multiple sclerosis.}, author={Nataly Urshansky and Karin Mausner-Fainberg and Eitan Auriel and Keren Regev and Firas Farhum and Arnon Karni}, journal={Journal of the neurological sciences}, year={2010}, volume={295 1-2}, pages={31-7} }