Back to Search
Start Over
Proteinase-activated receptor-2 agonist activates anti-influenza mechanisms and modulates IFNγ-induced antiviral pathways in human neutrophils.
- Source :
-
BioMed research international [Biomed Res Int] 2013; Vol. 2013, pp. 879080. Date of Electronic Publication: 2013 Sep 22. - Publication Year :
- 2013
-
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 IFNγ-induced antiviral responses of human leukocytes. However, the precise cellular antiviral defense mechanisms triggered in leukocytes after stimulation with IFNγ 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 IFNγ-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, IFNγ 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 IFNγ in neutrophils. Altogether, these findings emphasize two PAR2-controlled antiviral mechanisms that are independent of or modulated by IFNγ.
- Subjects :
- 2',5'-Oligoadenylate Synthetase genetics
Cell Degranulation
Humans
Immunity, Cellular
Influenza A virus genetics
Influenza A virus physiology
Myxovirus Resistance Proteins genetics
Neutrophils immunology
Oligopeptides pharmacology
Peroxidase metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Reactive Oxygen Species metabolism
Viral Nonstructural Proteins genetics
Virus Replication
Influenza A virus immunology
Interferon-gamma immunology
Neutrophils drug effects
Neutrophils physiology
Receptor, PAR-2 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2013
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 24171176
- Full Text :
- https://doi.org/10.1155/2013/879080