SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:lup.lub.lu.se:80c1670a-3f47-449a-a218-a5eed00ac8af"
 

Search: onr:"swepub:oai:lup.lub.lu.se:80c1670a-3f47-449a-a218-a5eed00ac8af" > Oxidised IL-33 driv...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Strickson, SamAstraZeneca, UK (author)

Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:80c1670a-3f47-449a-a218-a5eed00ac8af
  • https://lup.lub.lu.se/record/80c1670a-3f47-449a-a218-a5eed00ac8afURI
  • https://doi.org/10.1183/13993003.02210-2022DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. Methods In vitro epithelial damage assays and three-dimensional, air–liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. Results We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. Conclusions Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and mucoobstructive features in COPD.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Houslay, Kirsty F.AstraZeneca, UK (author)
  • Negri, Victor A.AstraZeneca, UK (author)
  • Ohne, YoichiroAstraZeneca, UK (author)
  • Ottosson, TomasAstraZeneca, Sweden (author)
  • Dodd, Roger B.AstraZeneca, UK (author)
  • Huntington, Catherine ChaillanAstraZeneca, UK (author)
  • Baker, TinaAstraZeneca, UK (author)
  • Li, JingjingAstraZeneca, UK (author)
  • Stephenson, Katherine E.AstraZeneca, UK (author)
  • O’Connor, Andy J.AstraZeneca, UK (author)
  • Sagawe, J. SophieAstraZeneca, UK (author)
  • Killick, HelenAstraZeneca, UK (author)
  • Moore, TomAstraZeneca, UK (author)
  • Rees, D. GarethAstraZeneca, UK (author)
  • Koch, SofiaAstraZeneca, UK (author)
  • Sanden, CarolineLund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups,Medetect AB(Swepub:lu)mphy-cgu (author)
  • Wang, YixinAstraZeneca, Sweden (author)
  • Gubbins, EliseAstraZeneca, UK (author)
  • Ghaedi, MahboobeAstraZeneca, UK (author)
  • Kolbeck, RolandAstraZeneca, UK (author)
  • Saumyaa, SaumyaaAstraZeneca, Sweden (author)
  • Erjefält, Jonas S.Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,DCD transplantation av lungor,Airway Inflammation and Immunology,Lund University Research Groups,DCD transplantation of lungs,Skåne University Hospital(Swepub:lu)mphy-jer (author)
  • Sims, Gary P.AstraZeneca, UK (author)
  • Humbles, Alison A.AstraZeneca, UK (author)
  • Scott, Ian C.AstraZeneca, UK (author)
  • Ros, Xavier RomeroAstraZeneca, UK (author)
  • Cohen, E. SuzanneAstraZeneca, UK (author)
  • AstraZeneca, UKAstraZeneca, Sweden (creator_code:org_t)

Related titles

  • In:European Respiratory Journal62:30903-1936

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view