Contribution of Protein Kinase D1 on Acute Pulmonary Inflammation and Hypersensitivity Pneumonitis Induced by Saccharopolyspora rectivirgula .

Autor:	Yoon TW; Integrated Biomedical Science Graduate Program, The University of Tennessee Health Science Center, Memphis, TN.; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN., Fitzpatrick EA; Integrated Biomedical Science Graduate Program, The University of Tennessee Health Science Center, Memphis, TN.; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN., Snyder JD; Integrated Biomedical Science Graduate Program, The University of Tennessee Health Science Center, Memphis, TN.; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN., Lee S; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN., Kim YI; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN; and., Zacheaus C; Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN., Yi AK; Integrated Biomedical Science Graduate Program, The University of Tennessee Health Science Center, Memphis, TN; ayi@uthsc.edu.; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN.; Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2022 Mar 10; Vol. 6 (3), pp. 224-242. Date of Electronic Publication: 2022 Mar 10.
DOI:	10.4049/immunohorizons.2200017
Abstrakt:	Protein kinase D1 (PKD1), a ubiquitously expressed serine/threonine kinase, regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, vesicle trafficking, Ag receptor signaling, and pattern recognition receptor signaling. We found previously that exposure to hypersensitivity pneumonitis (HP) inciting Ag Saccharopolyspora rectivirgula leads to the activation of PKD1 in a MyD88-dependent manner in various types of murine cells in vitro and in the mouse lung in vivo. However, it is currently unknown whether PKD1 plays a role in the S. rectivirgula -induced HP. In this study, we investigated contributions of PKD1 on the S. rectivirgula -induced HP using conditional PKD1-insufficient mice. Compared to control PKD1-sufficient mice, PKD1-insufficient mice showed substantially suppressed activation of MAPKs and NF-κB, expression of cytokines and chemokines, and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula The significantly reduced levels of alveolitis, MHC class II surface expression on neutrophils and macrophages, and IL-17A and CXCL9 expression in lung tissue were observed in the PKD1-insufficient mice repeatedly exposed to S. rectivirgula for 5 wk. PKD1-insuficient mice exposed to S. rectivirgula for 5 wk also showed reduced granuloma formation. Our results demonstrate that PKD1 plays an essential role in the initial proinflammatory responses and neutrophil influx in the lung after exposure to S. rectivirgula and substantially contribute to the development of HP caused by repeated exposure to S. rectivirgula Our findings suggest that PKD1 can be an attractive new molecular target for therapy of S. rectivirgula -induced HP. (Copyright © 2022 The Authors.)
Databáze:	MEDLINE
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