Feld Micha, Shpacovitch Victoria M, Ehrhardt Christina, Kerkhoff Claus, Hollenberg Morley D, Vergnolle Nathalie, Ludwig Stephan, Steinhoff Martin
Department of Dermatology and Ludwig-Boltzmann-Institute for Immunobiology of the Skin, University of Münster, Münster, Germany.
J Immunol. 2008 May 15;180(10):6903-10. doi: 10.4049/jimmunol.180.10.6903.
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.
蛋白酶激活受体-2（PAR(2)）在不同类型的人类白细胞中表达，并参与炎症和感染性疾病的发展。然而，其在病毒感染期间对人类单核细胞和巨噬细胞功能调节的确切作用仍不清楚。此外，PAR(2)激动剂在感染或炎症期间增强免疫介质诱导的效应的能力仍未得到充分研究。因此，我们研究了PAR(2)激动剂增强干扰素-γ（IFN-γ）诱导的人类单核细胞中甲型流感病毒复制抑制的能力。我们发现，在用PAR(2)激动剂和IFN-γ共同刺激细胞后，这种效应与IκBα丰度增加相关。值得注意的是，PAR(2)激动剂和IFN-γ的共同应用还增强了IFN-γ对人类单核细胞中IFN-γ诱导蛋白10 kDa释放以及CD64和αVβ3表面表达的影响。总之，这些发现表明PAR(2)激活在甲型流感病毒感染进展过程中具有潜在的保护作用。这种效应可能与PAR(2)激动剂增强IFN-γ对人类单核细胞的保护作用的能力有关。
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