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Interferon-β defici...
Interferon-β deficiency at asthma exacerbation promotes MLKL mediated necroptosis
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- Cerps, Samuel C. (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Menzel, Mandy (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Mahmutovic Persson, Irma (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Bjermer, Leif (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Akbarshahi, Hamid (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Immunopharmacology,Lund University Research Groups,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Uller, Lena (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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(creator_code:org_t)
- 2018-03-09
- 2018
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
- Related links:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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Abstract
Subject headings
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- Defective production of antiviral interferon (IFN)-β is thought to contribute to rhinovirus-induced asthma exacerbations. These exacerbations are associated with elevated lung levels of lactate dehydrogenase (LDH), indicating occurrence of cell necrosis. We thus hypothesized that reduced lung IFN-β could contribute to necrotic cell death in a model of asthma exacerbations. Wild-type and IFN-β-/- mice were given saline or house dust mite (HDM) intranasally for 3 weeks to induce inflammation. Double-stranded RNA (dsRNA) was then given for additional 3 days to induce exacerbation. HDM induced an eosinophilic inflammation, which was not associated with increased expression of cleaved caspase-3, cleaved PARP or elevated bronchoalveolar lavage fluid (BALF) LDH levels in wild-type. However, exacerbation evoked by HDM + dsRNA challenges increased BALF levels of LDH, apoptotic markers and the necroptotic markers receptor-interacting protein (RIP)-3 and phosphorylation of mixed linage kinase domain-like protein (pMLKL), compared to HDM + saline. Absence of IFN-β at exacerbation further increased BALF LDH and protein expression of pMLKL compared to wild-type. We demonstrate that cell death markers are increased at viral stimulus-induced exacerbation in mouse lungs, and that absence of IFN-β augments markers of necroptotic cell death at exacerbation. Our data thus suggest a novel role of deficient IFN-β production at viral-induced exacerbation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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