TY - JOUR
T1 - Dysregulated neurotrophin mRNA production by immune cells of patients with relapsing remitting multiple sclerosis
AU - Urshansky, Nataly
AU - Mausner-Fainberg, Karin
AU - Auriel, Eitan
AU - Regev, Keren
AU - Farhum, Firas
AU - Karni, Arnon
PY - 2010/8/15
Y1 - 2010/8/15
N2 - 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-β 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-β mRNA in HC. BDNF mRNA was similarly produced in monocytes and T cells in the HC group. The cytokines TNF-α 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-β-treated RR-MS patients and the HC were smaller.
AB - 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-β 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-β mRNA in HC. BDNF mRNA was similarly produced in monocytes and T cells in the HC group. The cytokines TNF-α 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-β-treated RR-MS patients and the HC were smaller.
KW - Cytokines
KW - Multiple sclerosis
KW - Neurotrophins
KW - mRNA
UR - https://www.scopus.com/pages/publications/77953872915
U2 - 10.1016/j.jns.2010.05.019
DO - 10.1016/j.jns.2010.05.019
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C2 - 20541775
AN - SCOPUS:77953872915
SN - 0022-510X
VL - 295
SP - 31
EP - 37
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -
