Source: International Congress 2016 – Asthma: mechanisms and biomarkers that promote clinical understanding
Disease area: Airway diseases

Abstract

IntroductionAsthma exacerbations commonly caused by respiratory viral infections lack efficient treatment options. Rhinovirus-induced exacerbations have been characterized by occurrence of necrotic cells, which may cause pathogenic effects. We hypothesized that house dust mite (HDM)-induced allergic inflammation primes the airway to aggravated responses to viral infection involving activation of cell death pathways (apoptosis, necrosis and necroptosis).MethodsExperimental asthma in mice was induced by 3 weeks challenge of HDM intranasally. dsRNA a viral mimic (or saline control) was given for additional 3 days to induce exacerbation. Lung tissue apoptosis was evaluated using western blot for cleaved caspase-3 and PARP together with TUNEL-staining on lung sections. BAL fluid LDH levels were used as marker of cell necrosis. Lung expression of RIP3 was determined to explore occurrence of necroptosis.ResultsThere was no evidence of cell death after 3 weeks of HDM exposures alone. Exacerbation evoked by dsRNA aggravated HDM-induced inflammation, increased LDH in BALF (p<0.05) and increased the apoptotic markers cleaved caspases-3 and PARP compared to control (p<0.05) and compared to non-allergic mice that received dsRNA. This was confirmed with TUNEL (mostly recruited cells). Increased expression (p<0.05) of RIP3 was induced by dsRNA without prior HDM challenge but was not further increased at exacerbation.ConclusionA mixture of both apoptotic and necrotic pathways are activated during exacerbation whereas allergen challenge alone did not induce these events. We suggest that cell death pathways are involved in driving asthma exacerbations and may thus be molecular targets for therapeutic intervention.


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Samuel Cerps (Lund, Sweden), Samuel Cerps, Mandy Menzel, Hamid Akbarshahi, Lena Uller. Increased levels of apoptotic and necrotic markers during asthma exacerbation. Eur Respir J 2016; 48: Suppl. 60, 573

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