Dietary DHA mitigates ozone induced pulmonary inflammation
膳食 DHA 可减轻臭氧引起的肺部炎症
基本信息
- 批准号:10360534
- 负责人:
- 金额:$ 54.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-20 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdverse effectsAir PollutantsAir PollutionAlveolar MacrophagesApoptoticAreaBiochemicalBiophysicsCell membraneCellsCholesterolChronic lung diseaseClinicalComplexConsumptionDataDietDietary AdministrationDocosahexaenoic AcidsDocosahexaenoic acid supplementDocosahexaenoic acid supplementationEnvironmental PollutantsExposure toFPR2 geneHealthImmunologyIn VitroIncidenceIndividualInflammationInflammatoryInflammatory ResponseInhalation ToxicologyInjuryIntakeKnockout MiceLinkLungMediatingMembraneMembrane MicrodomainsMicroscopyMorbidity - disease rateMusNutrientNutritional BiochemistryOmega-3 Fatty AcidsOutcomeOzonePhenotypePopulationProductionPublic HealthPulmonary InflammationRecommendationReportingResolutionRoleSignal TransductionSorting - Cell MovementSourceStructureTLR4 geneTestingTherapeuticair filterbasechemokinecytokinedietaryhuman modelimaging approachimprovedinnovationlipid mediatorlipidomicslung injurymacrophagemethyl-beta-cyclodextrinmultidisciplinarynovel therapeutic interventionozone exposurepreventquantitative imagingreceptorrecruittargeted treatmentwestern diet
项目摘要
PROJECT SUMMARY
Premise and hypothesis: Ozone (O3) is a criteria air pollutant that increases the incidence of chronic
pulmonary diseases. The detrimental health effects upon O3 exposure occur in part through pulmonary
inflammation initiated by alveolar macrophage production of cytokine/chemokines. O3-induced inflammation
in the alveolar macrophage is driven by toll-like receptor 4 (TLR4), that increases NFB activation and
subsequent production of proinflammatory cytokines. Therefore, targeting TLR4 driven signaling in
alveolar macrophages is a viable target to mitigate O3-induced pulmonary inflammation. In this
application, we focus on the role of diet in regulating alveolar macrophage TLR4-mediated
inflammatory responses upon O3 exposure. Specifically, dietary docosahexaenoic acid (DHA), an
omega-3 polyunsaturated fatty acid that is poorly consumed in the western diet, may protect against O3-
induced pulmonary inflammation. Based on strong preliminary data, we propose the central hypothesis
that DHA suppresses and resolves pulmonary inflammation through two distinct mechanisms: 1) Structurally,
we propose that DHA acyl chains of the plasma membrane remodel the size and composition of alveolar
macrophage lipid rafts to suppress downstream signaling and cytokine secretion; 2) Biochemically, DHA
undergoes enzymatic conversion into specialized pro-resolving lipid mediators (SPM), which are
highly potent immunoresolvants. As a consequence, DHA-derived SPMs decrease NFB activation
and the production of proinflammatory cyto/chemokines while promoting the clearance of apoptotic
cells termed ‘efferocytosis’. The hypothesis is supported by preliminary data to show that DHA
decreases murine O3 induced pulmonary inflammation, augments levels of SPMs while increasing
expression of the SPM receptor ALX/FPR2, and remodels lipid raft size in vitro. Approach: To
define the structural and biochemical mechanisms of DHA, we propose three aims. In Aim 1, we
will demonstrate that DHA improves O3-induced pulmonary inflammation and resolution of injury through
the use of DHA supplementation and a DHA-deficient mouse. In Aim 2, we will establish the mechanism
by which DHA remodels the biophysical structure of lipid rafts of alveolar macrophages to suppress
downstream signaling using cutting-edge quantitative imaging approaches. In Aim 3, we will establish
how DHA improves O3-induced pulmonary inflammation through the production of SPMs including the
use of an ALX/FPR knockout mouse. The proposed aims will innovatively merge inhalation
toxicology, nutritional biochemistry, membrane biophysics, and immunology. Impact:
Completion of this proposal will: 1) provide the scientific rationale for clinical DHA supplementation
studies mitigating O3-induced morbidity and; 2) provide key mechanistic links between
environmental pollutant exposure and diet that will inform targeted therapeutic strategies. Collectively, this
application is of high priority given that it sets the basis for long-term improved dietary
recommendations for susceptible populations in nonattainment air pollution areas to mitigate detrimental
health effects.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kymberly Mae Gowdy其他文献
Kymberly Mae Gowdy的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kymberly Mae Gowdy', 18)}}的其他基金
Dietary DHA mitigates ozone induced pulmonary inflammation
膳食 DHA 可减轻臭氧引起的肺部炎症
- 批准号:
10563167 - 财政年份:2020
- 资助金额:
$ 54.89万 - 项目类别:
Dietary EPA mitigates ozone induced pulmonary inflammation through ChemR23 signaling
膳食 EPA 通过 ChemR23 信号传导减轻臭氧引起的肺部炎症
- 批准号:
10506938 - 财政年份:2020
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
10170356 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
10408766 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
10158675 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
9762914 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
10290075 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
Novel role for CD163 in ozone induced alterations of pulmonary immunity
CD163 在臭氧诱导的肺免疫改变中的新作用
- 批准号:
10622014 - 财政年份:2018
- 资助金额:
$ 54.89万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 54.89万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 54.89万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 54.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 54.89万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
- 批准号:
RGPIN-2018-04753 - 财政年份:2022
- 资助金额:
$ 54.89万 - 项目类别:
Discovery Grants Program - Individual