title: Agonists of proteinase-activated receptor-2 enhance IFN-gamma-inducible effects on human monocytes: role in influenza A infection.
abstract: Proteinase-activated receptor-2 (PAR(2)) is expressed by different types of human leukocytes and involved in the development of inflammatory and infectious diseases. However, its precise role in the regulation of human monocyte and macrophage function during viral infection remains unclear. Also, the ability of PAR(2) agonists to enhance the effects induced by immune mediators during infection or inflammation is still poorly investigated. Therefore, we investigated the ability of a PAR(2) agonist to enhance IFN-gamma-induced suppression of influenza A virus replication in human monocytes. We found that this effect correlates with an increased abundance of IkappaBalpha after costimulation of cells with PAR(2) agonist and IFN-gamma. Remarkably, coapplication of PAR(2) agonist and IFN-gamma also enhances the effects of IFN-gamma on IFN-gamma-inducible protein 10 kDa release, and CD64 and alphaVbeta3 surface expression by human monocytes. Together, these findings indicate a potentially protective role of PAR(2) activation during the progression of influenza A virus infection. This effect could be associated with the ability of PAR(2) agonists to enhance IFN-gamma-induced protective effects on human monocytes.
authors.affiliation: Department of Dermatology and Ludwig-Boltzmann-Institute for Immunobiology of the Skin, University of Münster, Münster, Germany.
authors.forename: Micha
authors.initials: M
authors.lastname: Feld
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Shpacovitch
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Claus
authors.initials: C
authors.lastname: Kerkhoff
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
mesh_terms: D015153:Blotting, Western; D054357:Chemokine CXCL10 / Q000378:metabolism; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D009980:Influenza A virus / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology*; D039661:Integrin beta3 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D044464:Receptor, PAR-2 / Q000819:agonists*; D017452:Receptors, IgG / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D054357:Chemokine CXCL10; D039661:Integrin beta3; D044464:Receptor, PAR-2; D017452:Receptors, IgG; D007371:Interferon-gamma; D051550:I-kappa B Kinase