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BioMed Research International
Volume 2013 (2013), Article ID 879080, 10 pages
http://dx.doi.org/10.1155/2013/879080
Research Article

Proteinase-Activated Receptor-2 Agonist Activates Anti-Influenza Mechanisms and Modulates IFNγ-Induced Antiviral Pathways in Human Neutrophils

1Department of Dermatology, Heinrich-Heine University, 40225 Düsseldorf, Germany
2Leibniz-Institute for Analytical Sciences (ISAS), 44139 Dortmund, Germany
3Institute of Molecular Virology, ZMBE, Westfälische Wilhelms-University of Münster, 48149 Münster, Germany
4Department of Dermatology and Boltzmann Institute for Immunobiology of the Skin, Westfälische Wilhelms-University of Münster, 48149 Münster, Germany
5Departments of Dermatology and Surgery, University of California San Francisco (UCSF), San Francisco, CA 94143, USA

Received 29 April 2013; Accepted 12 August 2013

Academic Editor: Richard Tucker

Copyright © 2013 Micha Feld et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.