Alcohol consumption and RSV infection in airway injury
饮酒和 RSV 感染导致气道损伤
基本信息
- 批准号:8764671
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-10-01 至 2015-09-30
- 项目状态:已结题
- 来源:
- 关键词:Acute bronchitisAddressAdultAlcohol consumptionAlcoholsAsthmaBacterial InfectionsBreathingCause of DeathCell LineCell-Cell AdhesionCellsChronicChronic BronchitisChronic Obstructive Airway DiseaseCiliaCystic FibrosisDiseaseElementsEpithelialEpithelial CellsEpitheliumFrequenciesFunctional disorderHealthcareHeavy DrinkingImmuneImmune responseInflammatoryInjuryLeadLungMediatingModelingMorbidity - disease rateMotorMucociliary ClearanceMusPatientsPhosphorylationPopulationProductionProtein IsoformsProtein Kinase CProteinsRegulationRespiratory Syncytial Virus InfectionsRespiratory syncytial virusRisk FactorsSmall Interfering RNASmokerSmokingTestingUnited StatesViralVirusVirus Diseasesairway epitheliumalcohol effectalcohol exposurealcohol responseantimicrobialbasecostcytotoxicityin vitro Modelin vivoin vivo Modelinhibitor/antagonistinjured airwaylink proteinmortalitymouse modelpathogenrepairedresearch studyrespiratoryrespiratory infection virusrespiratory virusresponsesurfactanttherapeutic targetvirus infection mechanism
项目摘要
DESCRIPTION (provided by applicant):
ABSTRACT Respiratory viral infections contribute to the pathophysiology of chronic obstructive pulmonary disease (COPD) exacerbations. COPD exacerbations represent a significant problem and cost to the VA. Respiratory virus infections are known to be more severe in heavy alcohol drinkers leading to post-viral secondary bacterial infections. Many studies have investigated the effect of alcohol on immune cell response, but no studies have addressed the mechanism(s) for alcohol exacerbation of host response to viruses at the level of the mucociliary transport apparatus. Inhaled respiratory viruses specifically infect the ciliated airway epithelia lining the lung airways, which contain the mucociliary apparatus and represents the first line of lung defense against such inhaled viruses. Mucociliary clearance is orchestrated via the beating action of the ciliated cells lining the airways. Respiratory viral infection of the ciliated epithelia results in the slowing of the ciliary beat frequency (CBF) and the detachment or loss of ciliated cells. While the stimulatory mechanisms of ciliary beating have been widely studied, little is known about agents and mechanisms that slow cilia beating or cause ciliated cells to detach. Many agents associated with decreased ciliary beating are capable of activating protein kinase C (PKC) in airway epithelial cells. Recently, we have observed that alcohol greatly potentiates cilia slowing and ciliated cell detachment in an in vivo mouse model of respiratory viral infection. Based on our observations, we hypothesize that: Alcohol potentiates airway viral infection injury by enhancing PKC5-dependent cilia slowing and detachment of ciliated cells. We will test this hypothesis by characterizing the impact of alcohol on respiratory syncytial virus (RSV) infection using an in vivo mouse exposure model, determining if PKC5 activity regulates ciliated cell detachment in airway epithelial cells from normal and PKC5(-/-) mice, and determining the mechanism of action for alcohol-mediated enhancement of cilia slowing and detachment in response to RSV. By exploiting the strengths of in vivo and in vitro models of cilia regulation, the experiments in these aims are intended to address key unanswered questions regarding how exposure to alcohol functions to disable the normal protective mucociliary clearance apparatus lining the airways leading to sustained and chronic inflammatory airway disease.
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation.
- DOI:10.1186/s12931-021-01799-5
- 发表时间:2021-07-15
- 期刊:
- 影响因子:5.8
- 作者:Warren KJ;Poole JA;Sweeter JM;DeVasure JM;Dickinson JD;Peebles RS Jr;Wyatt TA
- 通讯作者:Wyatt TA
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Todd A Wyatt其他文献
Todd A Wyatt的其他文献
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Alcohol consumption and RSV infection in airway injury
饮酒和 RSV 感染导致气道损伤
- 批准号:
8391585 - 财政年份:2011
- 资助金额:
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