Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis

Inflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.Bronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.Hematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function

Embodied learning via a knowledge concert: An exploratory intervention study

Background: Music listening can improve acquisition of new knowledge. Purpose: The purpose of the study was to evaluate the emotional and cognitive effects of a knowledge concerton the attending audience. Methodology: The audience was asked to complete a Visual Analogue Scale (10 cm) before and after listening to the concert, along five variables: Arousal, Degree of happiness, Degree of worry, Daily worries and Benevolence. Follow-up qualitative interviews gathered narratives from the participants. Findings: 228 concert attendees took part in the study by completing the questionnaires (51 percent of the whole audience). Statistically significant changes were observed in the outcome measures for: Arousal (p=0.002), Daily worries (p<0.001) and Degree of happiness (p=0.01). Degree of worry interacted with age (p<0.001). No changes were found for Benevolence (p=0.93). Gender and previous music experiences did not make a difference to feelings evoked by the music. Age, however, was important since younger participants became more worried by the concert than older. Originality: We discuss the potential role of future knowledge concerts that comprise qualities explored, such as mitigating a variety of embodied psychological capacities, including reflection and agency in audiences, facilitating learning about sensitive issues, and potentially also transformation towards prosocial mindsets and behavior

Dust

International audienceThis chapter provides guidelines to forecasters to predict dust storms and episodes of dust haze, typically caused by southward advection of large amounts of dust from the Sahara into the southern parts of West Africa. An important source of information for forecasting dust storms or haze is the three-hourly surface synoptic observation (SYNOP), hourly meteorological aviation routine weather report (METAR) and SPECI airport reports network in West Africa. The Spinning Enhanced Visible and InfraRed Imager (SEVIRI) infrared (IR) dust product is the most widely used for operational dust forecasting owing to its near-real-time availability, high time resolution and applicability during day and night. The chapter explains how best to use the data from station observations, remote sensing and numerical models in an operational forecast environment for the two main seasons (November-April Harmattan dust haze (HDH) and April-August convective dust storms in the Sahel)

Influence of gender and interleukin-10 deficiency on the inflammatory response during lung infection with Pseudomonas aeruginosa in mice

Cystic fibrosis females have a worse prognosis compared to male patients. Furthermore, cystic fibrosis patients infected with Pseudomonas aeruginosa have been shown to have dysregulated cytokine profiles, as higher levels of tumour necrosis factor alpha (TNF-α), interleukin (IL)-8, and lower levels of IL-10 are found in the bronchoalveolar lavage fluid compared to healthy controls. The present study was aimed at investigating the importance of gender and IL-10 in the susceptibility of C57BL/6 mice to pulmonary infection with Pseudomonas aeruginosa. We found that wildtype females were more susceptible than males to infection, as we observed greater weight loss, higher bacterial load, and inflammatory mediators in their lungs. IL-10 knockout mice, both females and males, had higher levels of TNF-α in the lungs compared to wildtype mice and maintained higher levels of polymorphonuclear cells and lower levels of macrophages for a longer period of time. Our results demonstrate that the number of bacteria recovered from the lungs of IL-10 knockout male mice was significantly higher than that observed in their wildtype male counterparts and we show that neutralization of IL-10 in infected female mice for a prolonged period of time leads to increased susceptibility to infection. Results reported in this study clearly demonstrate that females, both wildtype and IL-10 knockout mice are more susceptible to Pseudomonas aeruginosa infection than males, and that they mount a stronger inflammatory response in the lungs