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PAR1 regulation of CXCL1 expression and neutrophil recruitment to the lung in mice infected with influenza A virus.
Antoniak, Silvio; Tatsumi, Kohei; Schmedes, Clare M; Egnatz, Grant J; Auriemma, Alyson C; Bharathi, Vanthana; Stokol, Tracy; Beck, Melinda A; Griffin, John H; Palumbo, Joseph S; Mackman, Nigel.
Afiliación
  • Antoniak S; Department of Pathology and Laboratory Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Tatsumi K; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Schmedes CM; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Egnatz GJ; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Auriemma AC; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Bharathi V; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
  • Stokol T; Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • Beck MA; Departments of Nutrition and Pediatrics, Gillings School of Global Public Health, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Griffin JH; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
  • Palumbo JS; Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Mackman N; Department of Medicine, Division of Hematology and Oncology, UNC Blood Research Institute, University of North Carolina, Chapel Hill, NC, USA.
J Thromb Haemost ; 19(4): 1103-1111, 2021 04.
Article en En | MEDLINE | ID: mdl-33346953
BACKGROUND: Protease-activated receptor 1 (PAR1) is expressed in various immune cells and in the lung. We showed that PAR1 plays a role in Coxsackievirus B3 infection by enhancing toll-like receptor 3-dependent interferon- ß expression in cardiac fibroblasts. OBJECTIVES: We investigated the role of PAR1 in a mouse model of influenza A virus (IAV) infection. METHODS: We used mice with either a global deficiency of PAR1, cell type-specific deficiencies of PAR1, or mutation of PAR1 at the R41 or R46 cleavage sites. RESULTS: PAR1-deficient mice had increased CXCL1 expression in the lung, increased neutrophil recruitment, increased protein levels in the bronchoalveolar lavage fluid, and increased mortality after IAV infection compared with control mice infected with IAV. Results from mice with cell type-specific deletion of PAR1 indicated that PAR1 expression by hematopoietic cells suppressed CXCL1 expression, whereas PAR1 expression by endothelial cells enhanced CXCL1 expression in response to IAV infection. PAR1 activation also enhanced polyinosinic:polycytodylic acid induction of interleukin-8 in a human endothelial cell line. Mutation of the R46 cleavage site of PAR1 was associated with increased CXCL1 expression in the lung in response to IAV infection, which suggested that R46 signaling suppresses CXCL1 expression. CONCLUSIONS: These results indicate that PAR1 expression by different cell types and activation by different proteases modulates the immune response during IAV infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Infecciones por Orthomyxoviridae Límite: Animals Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Infecciones por Orthomyxoviridae Límite: Animals Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido