18 research outputs found
Targeting IL-1β and IL-17A driven inflammation during influenza-induced exacerbations of chronic lung inflammation.
For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation
Avaliação da diversidade fenotípica em rambuteiras (Nephelium lappaceum) com base na qualidade dos frutos
Can medicines development improve outcomes in asthma and chronic obstructive pulmonary disease management by driving effectiveness?
Chemical, physico-chemical and sensory characterization of mixed açai (Euterpe oleracea) and cocoa´s honey (Theobroma cacao) jellies
Usefulness of alveoscopy in the diagnosis of pneumocystis jiroveci pneumonia in HIV + patients
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Enraizamento e crescimento de estacas herbáceas do cacaueiro (clones Cepec 42, tsh 516 e tsh 1188) em função da aplicação do ácido indolbutírico (AIB)
Usefulness of Bronchoscopic Probe-Based Confocal Laser Endomicroscopy in the Diagnosis of <b><i>Pneumocystis jirovecii</i></b> Pneumonia
Fenologia da floração da nogueira macadâmia (Macadamia integrifolia Maiden & Betche) nas condições climáticas de Jaboticabal, São Paulo, Brasil
Respiratory Infections Cause the Release of Extracellular Vesicles: Implications in Exacerbation of Asthma/COPD
Background Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations. Methods To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis. Results Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia. Conclusions This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area