title: Role of proteinase-activated receptor-2 in anti-bacterial and immunomodulatory effects of interferon-γ on human neutrophils and monocytes.
abstract: Recent studies show that proteinase-activated receptor-2 (PAR(2)) contributes to the development of inflammatory responses. However, investigations into the precise role of PAR(2) activation in the anti-microbial defence of human leucocytes are just beginning. We therefore evaluated the contribution of PAR(2) to the anti-microbial response of isolated human innate immune cells. We found that PAR(2) agonist, acting alone, enhances phagocytosis of Staphylococcus aureus and killing of Escherichia coli by human leucocytes, and that the magnitude of the effect is similar to that of interferon-γ (IFN-γ). However, co-application of PAR(2) -cAP and IFN-γ did not enhance the phagocytic and bacteria-killing activity of leucocytes beyond that triggered by either agonist alone. On the other hand, IFN-γ enhances PAR(2) agonist-induced monocyte chemoattractant protein 1 (MCP-1) secretion by human neutrophils and monocytes. Furthermore, phosphoinositide-3 kinase and janus kinase molecules are involved in the synergistic effect of PAR(2) agonist and IFN-γ on MCP-1 secretion. Our findings suggest a potentially protective role of PAR(2) agonists in the anti-microbial defence established by human monocytes and neutrophils.
authors.affiliation: Department of Dermatology, IZKF Münster, Boltzmann Institute for Immunobiology of the Skin, University of Münster, Germany. vshpacovi@googlemail.com
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Shpacovitch
authors.forename: Micha
authors.initials: M
authors.lastname: Feld
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
authors.forename: Makiko
authors.initials: M
authors.lastname: Kido
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Thomas
authors.initials: T
authors.lastname: Luger
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000819:agonists / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D044464:Receptor, PAR-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007155:Immunologic Factors; D044464:Receptor, PAR-2; D011994:Recombinant Proteins; D007371:Interferon-gamma