Implication of the toll-like receptor 4 pathway in the response to interferon-β in multiple sclerosis
| Autor: | Carmen Espejo, María A. Moro, Xavier Montalban, M.C. Edo, María José Mansilla, Nicolás Fissolo, Jordi Río, Carme Martínez Costa, Manuel Comabella, Marta F. Bustamante, Ignacio Lizasoain |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Multiple Sclerosis Real-Time Polymerase Chain Reaction Peripheral blood mononuclear cell Flow cytometry Cohort Studies medicine Humans Immunologic Factors Receptor Toll-like receptor medicine.diagnostic_test business.industry Multiple sclerosis Interferon-beta Middle Aged Flow Cytometry medicine.disease Toll-Like Receptor 4 Treatment Outcome Real-time polymerase chain reaction Neurology Interferon Type I Immunology Leukocytes Mononuclear TLR4 Female Neurology (clinical) Signal transduction business Signal Transduction |
| Zdroj: | Annals of Neurology. 70:634-645 |
| ISSN: | 0364-5134 |
| Popis: | Objective: Interferon-beta (IFNβ) has demonstrated beneficial effects reducing disease activity in multiple sclerosis (MS) patients, but a relatively large proportion of patients do not respond to treatment. Here we aimed to investigate the roles of the Toll-like receptor 4 (TLR4) and the type I IFN pathways in the response to IFNβ in MS patients. Methods: The expression levels of several components of the TLR4 and the type I IFN pathways were determined by flow cytometry and real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMCs) from a cohort of 85 MS patients treated for at least 2 years with IFNβ and classified into responders, intermediate responders, and nonresponders based on their clinical response to treatment. Thirty-two healthy controls were also included in the study for comparison purposes. Results: Compared to responders and controls, PBMCs from nonresponders and intermediate responders were characterized by increased baseline expression levels of endogenous IFNβ and elevated IFN receptor 1 (IFNAR1) expression in monocytes. Furthermore, the capacity of IFNβ to induce its own expression was deficient in cells from nonresponders compared with responders. Baseline expression of the interleukin-1 receptor-associated kinase 3 (IRAK3), a negative regulator of TLR4 signaling primarily expressed in monocytes, was found to be significantly decreased in IFNβ responders compared with nonresponders. Interpretation: These findings provide evidence of the involvement of the TLR4 and type I IFN signaling pathways in the response to IFNβ. ANN NEUROL 2011;70:634–645 |
| Databáze: | OpenAIRE |
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