D101. MECHANISTIC STUDIES OF LUNG INJURY AND REPAIR最新文献

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Transient Receptor Potential Vanilloid 4 (TRPV4) Protects the Lung from Bacterial Pneumonia via MAPK Molecular Switching 瞬时受体电位香草样蛋白4 (TRPV4)通过MAPK分子开关保护肺部免受细菌性肺炎
D101. MECHANISTIC STUDIES OF LUNG INJURY AND REPAIR Pub Date : 2020-05-01 DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7704
R. Scheraga, Susamma Abraham, L. Grove, B. Southern, J. Crish, J. Hasday, M. Olman
{"title":"Transient Receptor Potential Vanilloid 4 (TRPV4) Protects the Lung from Bacterial Pneumonia via MAPK Molecular Switching","authors":"R. Scheraga, Susamma Abraham, L. Grove, B. Southern, J. Crish, J. Hasday, M. Olman","doi":"10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7704","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7704","url":null,"abstract":"\u0000 Mechanical cell-matrix interactions can drive the innate immune responses to infection, however the molecular underpinnings of these responses remain elusive. We have discovered that the biophysical properties of the matrix in the range of injured fibrotic lung (≥ 25 kPa) conditions the macrophage response to LPS and infection respectively through the mechanosensitive cation channel, TRPV4 in vitro and in vivo. Studies suggest that LPS-induced macrophage activation is controlled in part by the MAPK pathway (i.e. p38, ERK, JNK). Thus, we investigated if TRPV4 plays a role in the macrophage activation response after LPS through alteration of the MAPK pathway. TRPV4 KO mice exhibited reduced lung bacterial clearance by macrophages (6-fold, p=0.012) after intratracheal P. aeruginosa administration and increased lung injury as measured by inflammatory cell infiltration (≥80±3%, p<0.05), vascular permeability (BAL total protein ≥63±6%, p<0.05), and pro-inflammatory cytokine secretion in BALF (IL-6, CCL2, CXCL1 ≥71±4%, p<0.05). LPS-induced p38 activation was decreased (69%, p<0.05) while JNK activation was increased (2-fold, p<0.05) in a stiffness-dependent manner with no change in ERK activation in TRPV4 KO BMDMs. Inhibition of p38 (SB203580, BIRB796) decreased phagocytosis whereas inhibition of JNK (SP600125) decreased cytokine secretion (IL-6, CCL2, and CXCL1) after LPS (2 fold, p<0.05). DUSP1/MKP1 (MAPK phosphatase) protein was reduced by 3-fold in TRPV4 KO and inhibition of DUSP1 decreased phagocytosis and selectively increased activation of JNK. These data are the first to demonstrate new roles for macrophage TRPV4 in regulating innate immunity in a mechanosensitive manner, through MAPK activation switching.","PeriodicalId":351773,"journal":{"name":"D101. MECHANISTIC STUDIES OF LUNG INJURY AND REPAIR","volume":"90 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123536569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen IL-17A和ifn - γ在葡萄球菌超抗原诱导的肺和肺外急性呼吸窘迫综合征中发挥着独特的作用
D101. MECHANISTIC STUDIES OF LUNG INJURY AND REPAIR Pub Date : 2020-05-01 DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7708
G. Rajagopalan, Sheryl L Coutermarsh-Ott, Y. Sun, B. Hu, Z. Harris, G. Stanley, J. Koff
{"title":"IL-17A and IFN-gamma Play Distinct Roles in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Induced by a Staphylococcal Superantigen","authors":"G. Rajagopalan, Sheryl L Coutermarsh-Ott, Y. Sun, B. Hu, Z. Harris, G. Stanley, J. Koff","doi":"10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7708","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7708","url":null,"abstract":"","PeriodicalId":351773,"journal":{"name":"D101. MECHANISTIC STUDIES OF LUNG INJURY AND REPAIR","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131179516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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