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Microglial regulation by astrocytes

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TitleInfo
Title
Microglial regulation by astrocytes
SubTitle
effect on CD40 surface expression and Its consequences for dendritic cell maturation
Name (type = personal)
NamePart (type = family)
Acevedo
NamePart (type = given)
Giselles Maria
NamePart (type = date)
1979-
DisplayForm
Giselles Acevedo
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Bonder
NamePart (type = given)
Edward M.
DisplayForm
Edward M. Bonder
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Jonakait
NamePart (type = given)
Gene Miller
DisplayForm
Gene Miller Jonakait
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Friedman
NamePart (type = given)
Wilma
DisplayForm
Wilma Friedman
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kim
NamePart (type = given)
Haesun
DisplayForm
Haesun Kim
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Ganea
NamePart (type = given)
Doina
DisplayForm
Doina Ganea
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - Newark
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2013
DateOther (qualifier = exact); (type = degree)
2013-01
CopyrightDate (encoding = marc); (point = start); (qualifier = exact)
2013
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Microglia are the primary immune-responsive cells in the central nervous system. Monocytically derived, they can be isolated in culture where, if stimulated by sequential treatment with granulocyte/monocyte colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS), they will upregulate the expression of major histocompatibility complex class II and surface levels of the co-stimulatory molecules CD40, CD80 and CD86 necessary for efficient antigen presentation and T cell activation. Hence, they assume a mature dendritic cell (DC) phenotype in isolation culture. In preliminary studies we have shown that the continued presence of astrocytes stunts the assumption of the microglial DC phenotype in a contact-dependent manner. The current study was designed to examine the mechanism(s) by which astrocytes prevent DC maturation in microglia. LPS signaling inhibitors SOCS1, SOCS3, TRIM30 and IRAK-M were rapidly and robustly upregulated by LPS treatment of co-cultured microglia. SOCS3 protein levels, however, were similar in both culture conditions while IRAK-M protein was elevated only in co-cultured cells. In IRAK-M-/- microglia CD11c levels were inhibited in both settings, but CD40 levels were only modestly affected. Expression of IFN, an inducer of both CD40 as well as inhibitors SOCS1 and SOCS3, was highest in isolated microglia, but neutralization of it affected only CD11c. GM-CSF pretreatment elicited a rapid and robust up-regulation of co-stimulatory molecules in isolated cells while subsequent LPS treatment increased expression primarily in co-cultured cells. CD40 and CD11c protein surface expression were maximal at the end of GM-CSF treatment in isolated cells while co-cultured cells awaited LPS signaling before placing protein on the cell surface. Differences in CD40 surface expression were not due to a more rapid mRNA or protein turnover. Rather, Western blots and flow cytometry showed that total CD40 protein levels in co-cultured microglia were high. These data suggested that CD40 protein was transcribed and translated but was retained intracellularly. Immunocytochemistry confirmed that CD40 was retained in the ER, but not in lysosomes or early endosomes. In conclusion, astrocytes affect particularly GM-CSF signaling of microglia. Future studies would be designed to address the mechanism(s) by which the extracellular environment created by astrocytes regulates the intracellular trafficking within microglia.
Subject (authority = RUETD)
Topic
Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4398
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
viii, 97 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Giselles Maria Acevedo
Subject (authority = ETD-LCSH)
Topic
Microglia
Subject (authority = ETD-LCSH)
Topic
Dendritic cells
Subject (authority = ETD-LCSH)
Topic
Astrocytes
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10002600001.ETD.000067586
RelatedItem (type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier (type = local)
rucore10002600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3KS6Q8V
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Acevedo
GivenName
Giselles
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-12-23 18:03:32
AssociatedEntity
Name
Giselles Acevedo
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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