title: Toll-like receptor 3 differently modulates inflammation in progressive or benign multiple sclerosis.
abstract: TLR-dependent signal transduction pathways were analyzed in patients with a diagnosis of either relapsing-remitting (RRMS), secondary progressive (PMS) or benign (BMS) MS and healthy controls (HC). Prototypical TLR molecules expressed either on the cell surface (TLR4) or intracellularly (TLR3) were stimulated with specific antigens (LPS and poly I:C, respectively). Expression of factors involved in TLR signaling cascades, production of downstream immune mediators and TLR expression were evaluated. Results showed that, whereas LPS-stimulation of TLR4 had a marginal effect on cell activation, poly I:C-stimulated TLR3 expression on immune cells was significantly increased in PMS and BMS compared to HC. This was associated with a higher responsiveness to poly I:C that resulted in the activation of the TLR3-mediated pathway and the production of inflammatory cytokines in PMS and, in contrast, in the up-regulation of a peculiar mosaic of inflammation-dampening genes in BMS. Results herein might explain different MS disease phenotypes.
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Marina
authors: M
authors: Saresella
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Andrea
authors: A
authors: Gatti
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Paola
authors: P
authors: Tortorella
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Ivana
authors: I
authors: Marventano
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Federica
authors: F
authors: Piancone
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Francesca
authors: F
authors: La Rosa
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Domenico
authors: D
authors: Caputo
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy.
authors: Marco
authors: M
authors: Rovaris
authors: Department of Clinical Sciences, University of Milano, 20100 Milano, Italy.
authors: Mara
authors: M
authors: Biasin
authors: Don C. Gnocchi Foundation, Pzza Morandi, 3, 20121 Milano, Italy; Department of Physiopathology and Transplants, University of Milano, 20100 Milano, Italy. Electronic address: mario.clerici@unimi.it.
authors: Mario
authors: M
authors: Clerici
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D010641:Phenotype; D011070:Poly I-C; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D011070:Poly I-C
keywords: Multiple sclerosis; Neuroinflammation; Signal transduction; TLR3; Toll like receptors