Novel Approaches for Improving Inflammation Resolution Following Chronic Exposure to Air Pollutants
Novel Approaches for Improving Inflammation Resolution Following Chronic Exposure to Air Pollutants
批准号:
10348421
负责人:
SRINIVASA T. Reddy
金额:
$48.86万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-03-01 至 2025-12-31
关键词:
AcuteAffectAir PollutantsAir PollutionAlzheimer&aposs DiseaseAnti-Inflammatory AgentsAntioxidantsApolipoprotein A-IArachidonic AcidsAromatic Polycyclic HydrocarbonsAtherosclerosisAttenuatedBiologicalBiologyBlood CirculationCellsCholatesChronicChronic DiseaseChronic Obstructive Pulmonary DiseaseDevelopmentDiabetes MellitusDiesel ExhaustDiseaseDisease modelEicosanoidsEnvironmental ExposureEnvironmental PollutantsEnzymesEpithelialEquilibriumExposure toFatty acid glycerol estersHigh Fat DietHomeostasisImpairmentInfectionInflammationInflammation MediatorsInflammatoryIntestinesKnock-outKnockout MiceKnowledgeLaboratoriesLesionLipidsMalignant NeoplasmsMediatingMediator of activation proteinMolecularMusMyelogenousObesityOrganoidsOxidative StressPTGS2 geneParkinson DiseasePathway interactionsPhenotypePhysiological ProcessesPlayProductionPropertyProstaglandinsPublic HealthPublishingRecoveryReportingResearchResolutionRoleSmall IntestinesTestingTissuesToxic Environmental SubstancesToxic effectWorkanalogbasechronic inflammatory diseasedietaryexperimental studyfight againstgut inflammationimmunoregulationimprovedin vivointestinal barrierintestinal epitheliumlipid mediatorlipid metabolismlipid transportlipoxin A4macrophagenovelnovel strategiesnovel therapeutic interventionnovel therapeuticsparticlepeptide Lpeptidomimeticsrepairedresponse to injurytissue repairultrafine particle
中文摘要
摘要
英文摘要
Abstract
Inflammation is a necessary biological response to injury, infection, and environmental exposures, and a well-
orchestrated physiological process, which if unchecked produces undesirable toxicity. Unresolved inflammation
contributes to the development of chronic diseases exacerbated by environmental exposures. The molecular
mechanisms and players of resolution of inflammation are not well understood. In this application, we will
examine two novel pathways that we hypothesize to play a critical role in the resolution of inflammation. 1. We
previously reported that diesel exhaust particle extracts and associated polycyclic aromatic hydrocarbons inhibit
COX2-dependent eicosanoid synthesis in murine macrophages. While COX2 is commonly thought to be pro-
inflammatory, Cox2 macrophage-specific knock-out (Cox2MKO) mice develop intestinal inflammation when fed
a high fat diet. Macrophage COX2 thus appears to provide an inhibitory molecular check on chronic inflammation
mediated by dietary and environmental exposures. In preliminary experiments, we show that loss of COX2
impaired efferocytosis in mouse primary macrophages and COX2 modulated the production of efferocytosis-
dependent lipid inflammatory mediators that not only affect secondary efferocytosis but also induce a tissue
repair phenotype in intestinal epithelial organoids. Under specific aim 1, based on published and recent
preliminary results, we will test the hypothesis that macrophage COX2-dependent eicosanoids play a critical role
in chronic inflammatory diseases exacerbated by environmental pollutants. 2. Our laboratory pioneered the
development of amphipathic peptides that mimic the antioxidant and anti-inflammatory properties of
apolipoprotein A-I (apoA-I). ApoA-I mimetic peptides (4F) inhibit the development of inflammatory diseases that
are exacerbated by dietary and environmental exposures including atherosclerosis and intestinal inflammation.
We demonstrated that 4F attenuates ambient ultrafine particle (UFP)-mediated oxidative stress, lipid metabolism,
atherosclerosis and intestinal inflammation. A common mechanism of protective action of 4F in all these disease
models is by tilting the net balance of lipid mediators of inflammation to an anti-inflammatory state, in the
circulation and tissues. In preliminary results, we demonstrated that apoA-I mimetic peptides enhance
transintestinal lipid transport (TILT) ex vivo and in vivo. Under specific aim 2, we will test the hypothesis that
TILT is a key mediator of resolution of inflammation and plays an important role in the development of chronic
inflammatory diseases exacerbated by environmental exposures. Successful completion of the studies proposed
in this new R01 application will not only advance our understanding of the biology and molecular mechanisms
underlying the effects of environmental exposures on the resolution of inflammation but also provide novel
therapeutic strategies in our fight against chronic inflammatory diseases exacerbated by air pollution.
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Novel Approaches for Improving Inflammation Resolution Following Chronic Exposure to Air Pollutants
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批准号:10581572
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项目类别:
-
资助金额:$47.23万
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财政年份:2022
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负责人:SRINIVASA T. Reddy
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依托单位:
Molecular profiling of pro-inflammatory HDL
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批准号:7584131
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项目类别:
-
资助金额:$38.63万
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财政年份:2007
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负责人:SRINIVASA T. Reddy
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依托单位:
Molecular profiling of pro-inflammatory HDL
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批准号:7263505
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项目类别:
-
资助金额:$38.63万
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财政年份:2007
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负责人:SRINIVASA T. Reddy
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依托单位:
Molecular profiling of pro-inflammatory HDL
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批准号:7392286
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项目类别:
-
资助金额:$38.63万
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财政年份:2007
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负责人:SRINIVASA T. Reddy
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依托单位:
Molecular profiling of pro-inflammatory HDL
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批准号:7789565
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项目类别:
-
资助金额:$38.63万
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财政年份:2007
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负责人:SRINIVASA T. Reddy
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依托单位:
PON2 and PON3 proteins in Atherosclerosis
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批准号:6560061
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项目类别:
-
资助金额:$36.81万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in atherosclerosis
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批准号:8703745
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项目类别:
-
资助金额:$37.73万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in atherosclerosis
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批准号:9066747
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项目类别:
-
资助金额:$38.5万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in atherosclerosis
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批准号:8854124
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项目类别:
-
资助金额:$37.92万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON-2 and PON3 proteins in atherosclerosis
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批准号:7643319
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项目类别:
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资助金额:$38.07万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON-2 and PON3 proteins in atherosclerosis
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批准号:7462402
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项目类别:
-
资助金额:$38.07万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in Atherosclerosis
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批准号:6692998
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项目类别:
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资助金额:$34.31万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in Atherosclerosis
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批准号:7002261
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项目类别:
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资助金额:$33.51万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in atherosclerosis
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批准号:8577944
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项目类别:
-
资助金额:$36.65万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON-2 and PON3 proteins in atherosclerosis
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批准号:7874509
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项目类别:
-
资助金额:$38.07万
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财政年份:2003
-
负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON-2 and PON3 proteins in atherosclerosis
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批准号:7317916
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项目类别:
-
资助金额:$38.07万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
The role of PON2 and PON3 proteins in Atherosclerosis
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批准号:6836025
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项目类别:
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资助金额:$34.31万
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财政年份:2003
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负责人:SRINIVASA T. Reddy
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依托单位:
海外基金