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Capacity of capsaze...
Capacity of capsazepinoids to relax human small airways and inhibit TLR3-induced TSLP and IFNβ production in diseased bronchial epithelial cells.
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- Mahmutovic Persson, Irma (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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Johansson, Martin (författare)
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- Brandelius, Angelica (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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- Bjermer, Leif (författare)
- 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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Yudina, Yuliana (författare)
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- Uller, Lena (författare)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
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Ingår i: International Immunopharmacology. - : Elsevier BV. - 1878-1705 .- 1567-5769. ; 13:3, s. 292-300
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Thymic stromal lymphopoietin (TSLP), an immunomodulating potentially disease-inducing cytokine, is overproduced in TLR3-stimulated bronchial epithelial cells from asthmatic donors whereas production of antiviral IFNβ is deficient. It is of therapeutic interest that capsazepine inhibits epithelial TSLP and relaxes human small airways with similar potencies. However, it is not known if other capsazepine-like compounds share such dual actions. This study explores epithelial anti-TSLP and anti-IFNβ effects of capsazepine and novel capsazepine-like bronchorelaxants. We used primary bronchial epithelial cells from asthmatic and chronic obstructive pulmonary disease (COPD) donors, and human small airways dissected from surgically removed lungs. Seven novel capsazepinoids were about 10 times, and one compound (RES187) >30 times, more potent than capsazepine as relaxants of LTD(4)-contracted small airways. TLR3-induced TSLP, TNFα, CXCL8, and IFNβ mRNA and protein levels were dose-dependently and non-selectively inhibited by capsazepine, equally in cells from asthmatic and COPD donors. The novel compounds, except RES187, reduced TSLP and IFNβ but none are more potent than capsazepine. Only capsazepine consistently inhibited TNFα and CXCL8 production and attenuated TLR3-induced epithelial NF-κB signalling. Hence, the present compounds did not separate between inhibition of TLR3-induced epithelial TSLP and IFNβ, but all compounds, except capsazepine, did separate between the bronchorelaxant and the epithelial immune effects. We conclude that similar mechanisms may be involved in capsazepine-like inhibition of TLR3-induced epithelial TSLP and IFNβ and that these are distinct from mechanisms involved in relaxation of small airways by these compounds.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Innate
- Inflammatory mediator
- Cytokines
- TSLP
- Asthma
- COPD
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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