Alzheimer (AD) disease is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as ...antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration.
In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications.
The growing body of evidence suggesting that microglia and astrocytes play a pathogenic role and activate inflammation pathways, the neurotoxic factors released by these cells when activated, and the way these factors may disrupt the homeostasis of the central nervous system all support the hypothesis that glia-induced inflammation exacerbates AD.
Inhibiting inflammation by deactivating glial cells may reduce the production of factors which contribute to neurotoxicity, and therefore result in clinical improvement. Microglia and astrocytes are therapeutic targets for the development of new drugs to combat this disease. Therapeutic strategies designed to counter the detrimental effects of overactivation of these cell populations should be investigated.
Resumen Introducción La enfermedad de Alzheimer (EA) es una compleja enfermedad neurodegenerativa caracterizada por inflamación, neurotoxicidad, estrés oxidativo y gliosis reactiva. La microglía y ...los astrocitos no solo actúan como células presentadoras de antígenos, sino que constituyen células efectoras, liberando moléculas proinflamatorias que promueven la excitotoxicidad y la neurodegeneración. Objetivo En la presente revisión bibliográfica se discute el papel de la glía, específicamente de la microglía y el astrocito en la fisiopatología de la EA y las posibles implicaciones terapéuticas. Desarrollo La emergente evidencia del papel patogénico y la activación de vías de inflamación a partir de la microglía y el astrocito, los factores neurotóxicos liberados por estas células cuando están activadas, y cómo estos pueden desestabilizar la homeostasis del sistema nervioso central, sostienen la idea de que la inflamación inducida por la glía amplifica la EA. Conclusiones La inhibición de la inflamación por inactivación de la glía, pudiera reducir la producción de factores que contribuyen con la toxicidad, resultando ser un beneficio clínico. La microglía y el astrocito constituyen blancos terapéuticos en el desarrollo de nuevos fármacos para combatir esta enfermedad. Estrategias terapéuticas diseñadas para contrarrestar el efecto perjudicial de la sobreactivación de estas poblaciones celulares deben ser investigadas.
Type I Interferon (IFN-α/β) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the
in vitro effects of IFN-α/β on ...peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-α, IFN-β treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-α, IFN-γ, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-β, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription–Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-α and IFN-β treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-γ expression after IFN-α but not after IFN-β treatments. The
in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.
Alzheimer disease (AD) is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as ...antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration.
In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications.
The growing body of evidence suggesting that microglia and astrocytes play a pathogenic role and activate inflammation pathways, the neurotoxic factors released by these cells when activated, and the way these factors may disrupt the homeostasis of the central nervous system all support the hypothesis that glia-induced inflammation exacerbates AD.
Inhibiting inflammation by deactivating glial cells may reduce the production of factors which contribute to neurotoxicity, and therefore result in clinical improvement. Microglia and astrocytes are therapeutic targets for the development of new drugs to combat this disease. Therapeutic strategies designed to counter the detrimental effects of overactivation of these cell populations should be investigated.
La enfermedad de Alzheimer (EA) es una compleja enfermedad neurodegenerativa caracterizada por inflamación, neurotoxicidad, estrés oxidativo y gliosis reactiva. La microglía y los astrocitos no solo actúan como células presentadoras de antígenos, sino que constituyen células efectoras, liberando moléculas proinflamatorias que promueven la excitotoxicidad y la neurodegeneración.
En la presente revisión bibliográfica se discute el papel de la glía, específicamente de la microglía y el astrocito en la fisiopatología de la EA y las posibles implicaciones terapéuticas.
La emergente evidencia del papel patogénico y la activación de vías de inflamación a partir de la microglía y el astrocito, los factores neurotóxicos liberados por estas células cuando están activadas, y cómo estos pueden desestabilizar la homeostasis del sistema nervioso central, sostienen la idea de que la inflamación inducida por la glía amplifica la EA.
La inhibición de la inflamación por inactivación de la glía, pudiera reducir la producción de factores que contribuyen con la toxicidad, resultando ser un beneficio clínico. La microglía y el astrocito constituyen blancos terapéuticos en el desarrollo de nuevos fármacos para combatir esta enfermedad. Estrategias terapéuticas diseñadas para contrarrestar el efecto perjudicial de la sobreactivación de estas poblaciones celulares deben ser investigadas.
Members of the Toll-like receptor (TLR) family probably play a fundamental role in pathogen recognition and activation of innate immunity. The present study used a systematic approach to analyze how ...different human leukocyte populations express specific transcripts for the first five characterized TLR family members. TLR1 was expressed in all leukocytes examined, including monocytes, polymorphonuclear leukocytes, T and B cells, and NK cells. In contrast TLR2, TLR4, and TLR5 were expressed in myelomonocytic elements. Exposure to bacterial products, such as LPS or lipoarabinomannan, or to proinflammatory cytokines increased TLR4 expression in monocytes and polymorphonuclear leukocytes, whereas IL-10 blocked this effect. TLR3 was only expressed in human dendritic cells (DC) wherein maturation induced by bacterial products or cytokines was associated with reduced expression. TLR3 mRNA expression was detected by in situ hybridization in DC and lymph nodes. These results demonstrate that TLR1 through TLR5 mRNAs are differentially expressed and regulated in human leukocytes. In particular, expression of TLR3 transcripts is restricted to DC that are the only elements which express the full TLR repertoire. These data suggest that TLR can be classified based on expression pattern as ubiquitous (TLR1), restricted (TLR2, TLR4, and TLR5 in myelomonocytic cells), and specific (TLR3 in DC) molecules.
The optic neuromyelitis or syndrome of Devic is an inflammatory and autoimmune illness of the central nervous system. It is characterized by attacks of optic neuritis and myelitis, being able to ...produce blindness, great neurological disability and even the short term death. Until the moment an effective treatment doesn't exist, the therapy is centred in the treatment of the acute attacks, the medical prevention of the complications and the rehabilitation. This article is a revision of this not very common illness, considering that its prevalence in our country has gone in increase. We compare between the optic neuromyelitis and the multiple sclerosis, being based on the main ones characteristic clinical-epidemic that distinguishes these two pathologies, considered by many clinical variants of oneself illness.
Immune response in optic neuromyelitis Lopategui Cabezas, I; Cervantes Llano, M; Pentón Rol, G
Anales de medicina interna (Madrid, Spain : 1984)
25, Issue:
7
Journal Article
Peer reviewed
The Optic Neuromyelitis is an inflammatory and autoimmune illness of the central nervous system. Presently work is carried out a revision of the different mechanisms involved in the pathogenesis of ...the Optic Neuromyelitis, the paper of the eosinophils is analyzed, of the antibodies against own antigens and of the regulatory T cells in the illness. In the Optic Neuromyelitis is very important the humoral response, the illness exists it is characterized by the immunocomplex deposit, activation of the complement, production of antibodies against proteins of the myelin and eosinophils recruitment in the lesions. It also exists an increase of the expression of chemokines receptors like the CCR3, specific of TH2 cells; the illness is associate predominantly to a TH2 response.
IFN-gamma is a potent activator of mononuclear phagocyte function and promotes the development of Th1 responses. Moreover, it induces and modulates chemokine production in a variety of cell types, ...including mononuclear phagocytes. In the present study, we examined the effect of IFN-gamma on the expression of CC chemokine receptors in human monocytes. IFN-gamma selectively and rapidly inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with an ED50 of approximately 50 U/ml. The effect was rapid (detectable after 1 h) and reversible. Other chemokine receptors (CCR1, CCR3, CCR4, and CCR5) were not substantially affected, and CXCR4 was reduced. IFN-gamma acted in concert with LPS, TNF-alpha, and IL-1beta in inhibiting CCR2 expression. IFN-gamma-treated monocytes showed a shorter half-life of CCR2 mRNA compared with untreated cells, whereas the rate of nuclear transcription was unaffected. The inhibition of CCR2 mRNA expression by IFN-gamma was associated with a lower number of surface receptors and lower chemotactic responsiveness. Thus, IFN-gamma, an inducer of MCP-1 and MCP-3 in mononuclear phagocytes, selectively inhibits expression of the MCP receptor CCR2 in monocytes. These results are consistent with an emerging paradigm of divergent regulation by several agents of chemokine production and receptor expression in monocytes. The inhibition of MCP-1R expression may serve as a means of retaining mononuclear phagocytes at sites of inflammation and as a feedback mechanism in the regulation of recruitment from the blood.
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