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Responses of mouse macrophages to oxidative stress

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TitleInfo
Title
Responses of mouse macrophages to oxidative stress
Name (type = personal)
NamePart (type = family)
Connor
NamePart (type = given)
Agnieszka
NamePart (type = date)
1971
DisplayForm
Agnieszka Connor
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Gerecke
NamePart (type = given)
Donald R.
DisplayForm
Donald R. Gerecke
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Gordon
NamePart (type = given)
Marion K.
DisplayForm
Marion K. Gordon
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Laskin
NamePart (type = given)
Jefferey D.
DisplayForm
Jefferey D. Laskin
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Laskin
NamePart (type = given)
Debra L.
DisplayForm
Debra L. Laskin
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Billack
NamePart (type = given)
Blase C.
DisplayForm
Blase C. Billack
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 - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2012
DateOther (qualifier = exact); (type = degree)
2012-10
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Tissue injury induced by infections or xenobiotics is associated with oxidative stress and inflammation, which are thought to contribute to pathogenic response. We hypothesized that toll-like receptor 4 (TLR4) is important in macrophage responsiveness to oxidative stress. To test this, we compared the response of TLR4 mutant C3H/HeJ mice and control C3H/HeOuJ mice to ozone and to bacterially-derived lipopolysaccharide (LPS). Exposure of C3H/HeOuJ mice to ozone (0.8 ppm for 3 h) resulted in increases in bronchoalveolar lavage lipocalin 24p3, 4-hydroxynonenal, surfactant protein-D, macrophage and protein content. Increased nuclear binding activity of NF-B and expression of TNF mRNA was also noted in lung macrophages. Findings that these responses to ozone were reduced in C3H/HeJ mice demonstrate that functional TLR4 contributes to ozone-induced injury, inflammation, and oxidative stress. We next determined if lung and liver macrophage responses to LPS are also mediated by TLR4. Treatment of control C3H/HeOuJ mice with LPS (3 mg/ml) resulted in increased numbers of macrophages in liver and lung after 48 h. In liver, but not lung macrophages, a rapid increase in mRNA expression of MnSOD and HO-1, as well as COX-2 and microsomal prostaglandin E synthase-1 was also observed. Conversely, macrophage COX-2 protein expression increased in both macrophage populations. The effects of LPS were significantly reduced in C3H/HeJ mice indicating TLR4 is also involved in LPS-induced oxidative stress, inflammation and macrophages activation in the liver and lung. To investigate mechanisms regulating macrophage responses, we evaluated the effects of hypoxia-induced oxidative stress on LPS-induced activation of macrophages using RAW 264.7 murine macrophages. Hypoxia augmented the effects of LPS on iNOS, COX-2, IL-1, GLUT-1 and VEGF-A mRNA expression. Hypoxia also upregulated LPS-induced protein expression of iNOS and COX-2, as well as MnSOD, lipocalin 24p3, and MMP-9. Some of these responses were dependent on p44/42 mitogen activated protein kinase signaling. Taken together, these studies demonstrate a key role of TLR4 in both sterile and infection driven inflammatory responses. These findings may be important in the development of effective therapeutics for treating diseases associated with prominent macrophages inflammatory responses.
Subject (authority = RUETD)
Topic
Toxicology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4259
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xv, 146 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Agnieszka Jankowska Connor
Subject (authority = ETD-LCSH)
Topic
Oxidative stress
Subject (authority = ETD-LCSH)
Topic
Anoxemia
Subject (authority = ETD-LCSH)
Topic
Mice as laboratory animals
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066660
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3HM577W
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
Connor
GivenName
Agnieszka
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-09-21 02:08:57
AssociatedEntity
Name
Agnieszka Connor
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2013-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2013.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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