tetano
Editor, Senior Moderator
Biomed Res Int. 2013;2013:879080. doi: 10.1155/2013/879080. Epub 2013 Sep 22.
Proteinase-Activated Receptor-2 Agonist Activates Anti-Influenza Mechanisms and Modulates IFN γ -Induced Antiviral Pathways in Human Neutrophils.
Feld M, Shpacovitch V, Ehrhardt C, Fastrich M, Goerge T, Ludwig S, Steinhoff M.
Source
Department of Dermatology, Heinrich-Heine University, 40225 D?sseldorf, Germany.
Abstract
Proteinase-activated receptor-2 (PAR2) is expressed by human leukocytes and participates in the development of inflammatory diseases. Recent studies demonstrated an ability of PAR2 agonist to enhance IFN γ -induced antiviral responses of human leukocytes. However, the precise cellular antiviral defense mechanisms triggered in leukocytes after stimulation with IFN γ and/or PAR2 agonist remain elusive. Therefore, we aimed to identify neutrophil defense mechanisms involved in antiviral resistance. Here we demonstrated that PAR2 agonist enhanced IFN γ -related reduction of influenza A virus (IAV) replication in human neutrophils. PAR2-mediated decrease in IAV replication was associated with reduced NS-1 transcription. Moreover, PAR2-dependent neutrophil activation resulted in enhanced myeloperoxidase degranulation and extracellular myeloperoxidase disrupted IAV. The production of ROS was elevated in response to PAR2 activation. Interestingly, IFN γ did not influence both effects: PAR2 agonist-triggered myeloperoxidase (MPO) release and reactive oxygen species (ROS) production, which are known to limit IAV infections. In contrast, orthomyxovirus resistance gene A (MxA) protein expression was synergistically elevated through PAR2 agonist and IFN γ in neutrophils. Altogether, these findings emphasize two PAR2-controlled antiviral mechanisms that are independent of or modulated by IFN γ .
PMID:
24171176
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24171176
Proteinase-Activated Receptor-2 Agonist Activates Anti-Influenza Mechanisms and Modulates IFN γ -Induced Antiviral Pathways in Human Neutrophils.
Feld M, Shpacovitch V, Ehrhardt C, Fastrich M, Goerge T, Ludwig S, Steinhoff M.
Source
Department of Dermatology, Heinrich-Heine University, 40225 D?sseldorf, Germany.
Abstract
Proteinase-activated receptor-2 (PAR2) is expressed by human leukocytes and participates in the development of inflammatory diseases. Recent studies demonstrated an ability of PAR2 agonist to enhance IFN γ -induced antiviral responses of human leukocytes. However, the precise cellular antiviral defense mechanisms triggered in leukocytes after stimulation with IFN γ and/or PAR2 agonist remain elusive. Therefore, we aimed to identify neutrophil defense mechanisms involved in antiviral resistance. Here we demonstrated that PAR2 agonist enhanced IFN γ -related reduction of influenza A virus (IAV) replication in human neutrophils. PAR2-mediated decrease in IAV replication was associated with reduced NS-1 transcription. Moreover, PAR2-dependent neutrophil activation resulted in enhanced myeloperoxidase degranulation and extracellular myeloperoxidase disrupted IAV. The production of ROS was elevated in response to PAR2 activation. Interestingly, IFN γ did not influence both effects: PAR2 agonist-triggered myeloperoxidase (MPO) release and reactive oxygen species (ROS) production, which are known to limit IAV infections. In contrast, orthomyxovirus resistance gene A (MxA) protein expression was synergistically elevated through PAR2 agonist and IFN γ in neutrophils. Altogether, these findings emphasize two PAR2-controlled antiviral mechanisms that are independent of or modulated by IFN γ .
PMID:
24171176
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24171176