2020
DOI: 10.3389/fimmu.2020.580401
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Inhibiting Protein Kinase D Promotes Airway Epithelial Barrier Integrity in Mouse Models of Influenza A Virus Infection

Abstract: RationaleProtein kinase D (PKD) is a serine/threonine kinase family that is involved in a wide array of signaling pathways. Although PKD has been implicated in immune responses, relatively little is known about the function of PKD in the lung or during viral infections.ObjectivesWe investigated the hypothesis that PKD is involved in multiple aspects of host response to viral infection.MethodsThe selective PKD inhibitor CRT0010166 was administered to C57BL/6 mice prior to and during challenge with either inhale… Show more

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Cited by 6 publications
(20 citation statements)
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“…To determine the role of PKD3 in this process, we next measured epithelial barrier function in WT and PKD3 −/− mice. In contrast to the barrier protection and reduced inflammation observed with CRT‐treated mice, 18 PKD3 −/− mice were not protected from poly(I:C)‐mediated inside‐out barrier disruption as seen by total protein and serum albumin leak into the airspace (Figure 2a). PKD3 −/− mice were also not protected from outside‐in barrier disruption as seen by loss of inhaled 4‐kDa FITC–dextran from the airspace and accumulation in the serum (Figure 2b).…”
Section: Resultsmentioning
confidence: 84%
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“…To determine the role of PKD3 in this process, we next measured epithelial barrier function in WT and PKD3 −/− mice. In contrast to the barrier protection and reduced inflammation observed with CRT‐treated mice, 18 PKD3 −/− mice were not protected from poly(I:C)‐mediated inside‐out barrier disruption as seen by total protein and serum albumin leak into the airspace (Figure 2a). PKD3 −/− mice were also not protected from outside‐in barrier disruption as seen by loss of inhaled 4‐kDa FITC–dextran from the airspace and accumulation in the serum (Figure 2b).…”
Section: Resultsmentioning
confidence: 84%
“…To determine whether PKD3 has a neutrophil‐intrinsic role in promoting neutrophil recruitment to the lung following dsRNA challenge, we generated a new line of mice by breeding PKD3‐floxed mice 18 with mice expressing Cre recombinase driven by the Ly6G promoter. Resulting dual transgenic PKD3‐floxed × Ly6G‐Cre mice were challenged with inhaled poly(I:C) and compared with single transgenic controls.…”
Section: Resultsmentioning
confidence: 99%
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“…Specific inhibition of these factors significantly alters the functions of specialized inflammatory cells suggesting that these factors may help in early diagnosis and could be predictors of clinical symptoms ( Guo et al, 2022a ). IDO1 is also an important immunomodulatory gene in T lymphocyte activation and in modulating immune tolerance ( Veazey et al, 2020 ; Makaremi et al, 2022 ). In preclinical models, pharmacological inhibitors of IDO1 have therapeutic utility in various diseases, including cancer, HIV and influenza ( Yang et al, 2020b ; Chang et al, 2020 ; Chi et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%