Cytokines and immunity in multiple sclerosis: the dual signal hypothesis

Martino, Gianvito; Furlan, Roberto; Brambilla, Elena; Bergami, A.; Ruffini, Francesca; Gironi, Maira; Poliani, Pietro Luigi; Grimaldi, Luigi M. E.; Comı, Gıancarlo

doi:10.1016/s0165-5728(00)00295-2

Cited by 53 publications

(27 citation statements)

References 31 publications

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“…Many of the p38 MAPK-controlled cytokines, such as IL-1␤ and IL-6, are elevated in MS (44)(45)(46)(47), and these cytokines are required to elicit EAE (48,49). Furthermore, neuroantigen-specific Th1 and Th17 responses associated with MS pathogenesis depend on p38 MAPK (see above).…”

Section: Multiple Roles Of P38 Mapk In Autoimmune Demyelination-emergmentioning

confidence: 99%

The Emerging Role of p38 Mitogen-Activated Protein Kinase in Multiple Sclerosis and Its Models

Krementsov

Thornton

Teuscher

et al. 2013

Molecular and Cellular Biology

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Multiple sclerosis (MS), the most common disabling neurologic disease of young adults, is considered a classical T cell-mediated disease and is characterized by demyelination, axonal damage, and progressive neurological dysfunction. The currently available disease-modifying therapies are limited in their efficacy, and improved understanding of new pathways contributing to disease pathogenesis could reveal additional novel therapeutic targets. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is known to be triggered by stress stimuli and to contribute to inflammatory responses. Importantly, a number of recent studies have identified this signaling pathway as a central player in MS and its principal animal model, experimental allergic encephalomyelitis. Here, we review the evidence from mouse and human studies supporting the role of p38 MAPK in regulating key immunopathogenic mechanisms underlying autoimmune inflammatory disease of the central nervous system and the potential of targeting this pathway as a disease-modifying therapy in MS. PATHOGENESIS OF MULTIPLE SCLEROSIS

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Section: Multiple Roles Of P38 Mapk In Autoimmune Demyelination-emergmentioning

confidence: 99%

The Emerging Role of p38 Mitogen-Activated Protein Kinase in Multiple Sclerosis and Its Models

Krementsov

Thornton

Teuscher

et al. 2013

Molecular and Cellular Biology

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“…CD4 as well as CD8 T cells have been shown to play a pathogenic role in various autoimmune diseases (2). Pathogenic T cells infiltrate the target organs and locally secrete proinflammatory cytokines and chemokines leading to tissue inflammation and possibly subsequent tissue destruction (3)(4)(5). Local presentation of autoantigens by MHC molecules in the target tissue of the autoimmune attack, i.e.…”

Section: Tandem Mass Spectrometry Was Used To Identify Naturally Procmentioning

confidence: 99%

Naturally Presented Peptides on Major Histocompatibility Complex I and II Molecules Eluted from Central Nervous System of Multiple Sclerosis Patients

Fissolo

Haag

Graaf

et al. 2009

Molecular & Cellular Proteomics

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Tandem mass spectrometry was used to identify naturally processed peptides bound to major histocompatibility complex (MHC) I and MHC II molecules in central nervous system (CNS) of eight patients with multiple sclerosis (MS). MHC molecules were purified from autopsy CNS material by immunoaffinity chromatography with monoclonal antibody directed against HLA-A, -B, -C, and -DR. Subsequently peptides were separated by reversedphase HPLC and analyzed by mass spectrometry. Database searches revealed 118 amino acid sequences from self-proteins eluted from MHC I molecules and 191 from MHC II molecules, corresponding to 174 identified source proteins. These sequences define previously known and potentially novel autoantigens in MS possibly involved in disease induction and antigen spreading. Taken together, we have initiated the characterization of the CNS-expressed MHC ligandome in CNS diseases and were able to demonstrate the presentation of naturally processed myelin basic protein peptides in the brain of MS patients.

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“…In MS, the pro-inflammatory cytokines TNFα, IL-1β and IL-6 are abnormally produced in the inflamed CNS and serum levels may be elevated [9,[11][12][13][14]. Expression of TNFα, IL-1β, and IL-6 is often co-regulated.…”

Section: Introductionmentioning

confidence: 99%