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TLR3/TAK1 signallin...
TLR3/TAK1 signalling regulates rhinovirus-induced interleukin-33 in bronchial smooth muscle cells
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- Ramu, Sangeetha (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Calvén, Jenny (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Michaeloudes, Charalambos (författare)
- Imperial College London
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- Menzel, Mandy (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Akbarshahi, Hamid (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translationell lungmedicin,Respiratory Immunopharmacology,Lund University Research Groups,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Translational Respiratory Medicine
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- Chung, Kian Fan (författare)
- Imperial College London
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- Uller, Lena (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Respiratory Immunopharmacology,Lund University Research Groups
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(creator_code:org_t)
- 2020-10-05
- 2020
- Engelska.
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://openres.ersj...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background: Asthma exacerbations are commonly associated with rhinovirus (RV) infection. Interleukin-33 (IL-33) plays an important role during exacerbation by enhancing Type 2 inflammation. Recently we showed that RV infects bronchial smooth muscle cells (BSMCs) triggering production of interferons and IL-33. Here we compared levels of RV-induced IL-33 in BSMCs from healthy and asthmatic subjects, and explored the involvement of pattern-recognition receptors (PRRs) and downstream signalling pathways in IL-33 expression.Method: BSMCs from healthy and severe and non-severe asthmatic patients were infected with RV1B or stimulated with the PRR agonists poly(I:C) (Toll-like receptor 3 (TLR3)), imiquimod (TLR7) and poly(I:C)/LyoVec (retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated protein 5 (MDA5)). Knockdown of TLR3, RIG-I and MDA5 was performed, and inhibitors targeting TBK1, nuclear factor-κB (NF-κB) and transforming growth factor (TGF)-β-activated kinase 1 (TAK1) were used. Gene and protein expression were assessed.Results: RV triggered IL-33 gene and protein expression in BSMCs. BSMCs from patients with non-severe asthma showed higher baseline and RV-induced IL-33 gene expression compared to cells from patients with severe asthma and healthy controls. Furthermore, RV-induced IL-33 expression in BSMCs from healthy and asthmatic individuals was attenuated by knockdown of TLR3. Inhibition of TAK1, but not NF-κB or TBK1, limited RV-induced IL-33. The cytokine secretion profile showed higher production of IL-33 in BSMCs from patients with non-severe asthma compared to healthy controls upon RV infection. In addition, BSMCs from patients with non-severe asthma had higher levels of RV-induced IL-8, TNF-α, IL-1β, IL-17A, IL-5 and IL-13.Conclusion: RV infection caused higher levels of IL-33 and increased pro-inflammatory and Type 2 cytokine release in BSMCs from patients with non-severe asthma. RV-induced IL-33 expression was mainly regulated by TLR3 and downstream via TAK1. These signalling molecules represent potential therapeutic targets for treating asthma exacerbations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
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- ref (ämneskategori)
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