01 μg/mL anti-CD3ε with graded numbers of MSCs and other reagents as described for individual experiments. Individual experiments were carried out between 2 and 7 times to ensure reproducibility. For culture experiments, individual conditions were generated in replicates of 3–6 and assayed separately. Results were expressed throughout as mean+SD and differences between conditions tested statistically by two-tailed, unpaired Student’s t-test. Significance was assigned at p<0.05. This study was supported by Science Foundation Ireland under grant numbers SFI PI 06/IN.1/B652

(M. D. G), SFI09/SRC/B1794 (M. D. G., J. M. M., F. B., B. P. M. and E. C.), by a Science Foundation Ireland Stoke’s Professorship (R. C.) and by the Health Research Board of Ireland under grant number HRB TRA/2007/04 (O. B.). Conflict of interest:

NVP-BGJ398 clinical trial The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“Ragweed pollen extract (RWE) possesses intrinsic NADPH oxidase activity that induces oxidative stress by initiating the production of intracellular reactive oxygen species (ROS). The AZD8055 chemical structure ROS are important contributors to the manifestation of allergic inflammation; furthermore, concomitant exposure to an allergen and an endotoxin trigger a stronger inflammatory response. One of the main pro-inflammatory cytokines produced in inflammatory responses is interleukin-1β (IL-1β), and its production is associated with caspase-1-containing inflammasome complexes. Intracellular ROS have been implicated in NLRP3 inflammasome-mediated IL-1β production, therefore, we aimed to study whether RWE influences the function of NLRP3 inflammasome. Here we describe that, in the presence

of NADPH, RWE significantly elevates lipopolysaccharide-induced IL-1β production of THP-1 cells as well as human primary macrophages and dendritic cells. We also demonstrate that increased IL-1β production is mediated through NLRP3 inflammasome in THP-1 macrophages. We provide evidence that RWE Metalloexopeptidase elevates cytosolic ROS level in these cells, and ROS inhibitors abolish IL-1β production. Furthermore, we show that RWE enhances lipopolysaccharide-induced gene transcription/expression of pro-IL-1β and key components of the inflammasome via a ROS-dependent mechanism. Ragweed (Ambrosia artemisiifolia) pollen is one of the most abundant aeroallergens that cause severe allergic symptoms. After hydration in rainwater, or in conditions with high humidity or moisture, ragweed pollen grains release sub-pollen particles of respirable size.[1] These particles can easily penetrate the lower airways and trigger or exacerbate asthma symptoms.