Irini Spyridaki1, Styliani Taka2, Chrysanthi Skevaki1,3,4,5, Aikaterini Trochoutsou1, Nikolaos G Papadopoulos1,6. 1. Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece. 2. Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece. staka@med.uoa.gr. 3. Institute of Laboratory Medicine, Philipps-Universität Marburg, Marburg, Germany. 4. Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität Marburg, Hannover, Germany. 5. German Center for Lung Research (DZL), Hannover, Germany. 6. Division of Infection, Inflammation and Respiratory Medicine, University of Manchester, Manchester, UK.
Abstract
INTRODUCTION: The leukotriene pathway may be implicated in the induction of virus-induced inflammation. Respiratory epithelial cells may express low levels of 5-lipoxygenase (5-LO) and release leukotrienes (LTs) C4, D4, and E4, upon exposure to viruses or other stimuli. Enhanced expression of 5-LO pathway proteins after rhinovirus (RV) infection has previously been described. We hypothesized that anti-leukotriene treatment of epithelial cells, with or without exposure to RV-infected peripheral blood mononuclear cells (PBMCs)-conditioned media, may inhibit RV-induced up-regulation of inflammatory cytokines. METHODS: PBMCs from a healthy donor were exposed to RV1B and supernatants were harvested at 48 h post infection. BEAS-2B cells were infected with RV, with or without conditioning with the PBMC supernatant. Treatment with anti-LT agents was performed either on both PBMCs and BEAS-2B or at the bronchial epithelial level only, with varying concentrations of montelukast (CysLT receptor antagonist) or MK-886 [FLAP(5-lipoxygenase-activating-protein) inhibitor]. Evaluation of the inflammatory cytokines IL-8, RANTES, IL-11, IL-6, and IP-10 was performed using ELISA. RESULTS: Our results show that anti-LT treatment of RV-infected bronchial epithelial cells suppresses epithelial RV-mediated cytokine production, independent of conditioning. CONCLUSIONS: This observation may represent an indirect mode of action of the anti-leukotrienes in virus-induced asthma.
INTRODUCTION: The leukotriene pathway may be implicated in the induction of virus-induced inflammation. Respiratory epithelial cells may express low levels of 5-lipoxygenase (5-LO) and release leukotrienes (LTs) C4, D4, and E4, upon exposure to viruses or other stimuli. Enhanced expression of 5-LO pathway proteins after rhinovirus (RV) infection has previously been described. We hypothesized that anti-leukotriene treatment of epithelial cells, with or without exposure to RV-infected peripheral blood mononuclear cells (PBMCs)-conditioned media, may inhibit RV-induced up-regulation of inflammatory cytokines. METHODS: PBMCs from a healthy donor were exposed to RV1B and supernatants were harvested at 48 h post infection. BEAS-2B cells were infected with RV, with or without conditioning with the PBMC supernatant. Treatment with anti-LT agents was performed either on both PBMCs and BEAS-2B or at the bronchial epithelial level only, with varying concentrations of montelukast (CysLT receptor antagonist) or MK-886 [FLAP(5-lipoxygenase-activating-protein) inhibitor]. Evaluation of the inflammatory cytokines IL-8, RANTES, IL-11, IL-6, and IP-10 was performed using ELISA. RESULTS: Our results show that anti-LT treatment of RV-infected bronchial epithelial cells suppresses epithelial RV-mediated cytokine production, independent of conditioning. CONCLUSIONS: This observation may represent an indirect mode of action of the anti-leukotrienes in virus-induced asthma.
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