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dc.contributor.author
Carniglia, Lila
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dc.contributor.author
Durand, Daniela Elizabeth
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dc.contributor.author
Caruso, Carla Mariana
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dc.contributor.author
Lasaga, Mercedes Isabel
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dc.date.available
2015-05-26T15:32:49Z
dc.date.issued
2013-02-26
dc.identifier.citation
Carniglia, Lila; Durand, Daniela Elizabeth; Caruso, Carla Mariana; Lasaga, Mercedes Isabel; Effect of NDP-a-MSH on PPAR-c and –b Expression and Anti-Inflammatory Cytokine Release in Rat Astrocytes and Microglia; Public Library Science; Plos One; 8; 2; 26-2-2013; 57313-57313;
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/546
dc.description.abstract
Brain inflammation plays a central role in numerous brain pathologies. Microglia and astrocytes are the main effector cells that become activated when an inflammatory process takes place within the central nervous system. a-melanocytestimulating hormone (a-MSH) is a neuropeptide with proven anti-inflammatory properties. It binds with highest affinity to the melanocortin receptor 4 (MC4R), which is present in astrocytes and upon activation triggers anti-inflammatory pathways. The aim of this research was to identify anti-inflammatory mediators that may participate in the
immunomodulatory effects of melanocortins in glial cells. Since peroxisome proliferator-activated receptors (PPARs) have
recently been implicated in the modulation of inflammation, we investigated the effect of an a-MSH analog, [Nle4
, D-Phe7]- a-MSH (NDP-a-MSH), on PPAR-b and PPAR-c gene and protein expression in rat primary astrocytes and microglia. We
initially demonstrated that rat primary microglia express MC4R and showed that treatment with NDP-a-MSH increases
PPAR-c protein levels and strongly decreases PPAR-b levels in both astrocytes and microglia. We also showed that
extracellular signal-regulated kinase 1/2 (ERK1/2)–mediated signaling is partially involved in these effects in a cell-specific fashion. Finally, we showed that NDP-a-MSH stimulates the release of the anti-inflammatory cytokines IL-10 and TGF-b from microglia and astrocytes, respectively. The presented data suggest a role for IL-10 and TGF-b in the protective action of melanocortins and a connection between MC4R pathway and that of the nuclear receptor PPAR-c. This is the first report providing evidence that MC4R is expressed in rat primary microglia and that melanocortins modulate PPAR levels in glial cells. Our findings provide new insights into the mechanisms underlying the activation of glial MC4R and open perspectives for new therapeutic strategies for the treatment of inflammation-mediated brain diseases.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Astrocytes
dc.subject
Microglia
dc.subject
Ndp-Alpha-Msh
dc.subject
Cytokines
dc.subject.classification
Ciencias Médicas y de la Salud
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dc.subject.classification
Medicina Básica
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dc.subject.classification
Neurociencias (incluye Psicofiosiología)
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dc.title
Effect of NDP-a-MSH on PPAR-c and –b Expression and Anti-Inflammatory Cytokine Release in Rat Astrocytes and Microglia
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/article
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dc.type
info:eu-repo/semantics/publishedVersion
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dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
8
dc.journal.number
2
dc.journal.pagination
57313-57313
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Carniglia, Lila. INSTITUTO DE INVESTIGACIONES BIOMEDICAS;
dc.description.fil
Fil: Durand, Daniela Elizabeth. INSTITUTO DE INVESTIGACIONES BIOMEDICAS;
dc.description.fil
Fil: Caruso, Carla Mariana. INSTITUTO DE INVESTIGACIONES BIOMEDICAS;
dc.description.fil
Fil: Lasaga, Mercedes Isabel. INSTITUTO DE INVESTIGACIONES BIOMEDICAS;
dc.journal.title
Plos One
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057313
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