title: 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.
authors.affiliation: Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Nataly
authors.initials: N
authors.lastname: Urshansky
authors.forename: Karin
authors.initials: K
authors.lastname: Mausner-Fainberg
authors.forename: Eitan
authors.initials: E
authors.lastname: Auriel
authors.forename: Keren
authors.initials: K
authors.lastname: Regev
authors.forename: Firas
authors.initials: F
authors.lastname: Farhum
authors.forename: Arnon
authors.initials: A
authors.lastname: Karni
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; D017252:CD3 Complex; D020381:Interleukin-17; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha