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Interleukin-33 is a...
Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage
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- Scott, Ian C. (författare)
- MedImmune Limited, Cambridge
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- Majithiya, Jayesh B. (författare)
- MedImmune Limited, Cambridge
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- Sanden, Caroline (författare)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Thornton, Peter (författare)
- AstraZeneca, UK
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- Sanders, Philip N. (författare)
- MedImmune Limited, Cambridge
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- Moore, Tom (författare)
- MedImmune Limited, Cambridge
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- Guscott, Molly (författare)
- MedImmune Limited, Cambridge
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- Corkill, Dominic J. (författare)
- MedImmune Limited, Cambridge
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- Erjefält, Jonas S. (författare)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Cohen, E. Suzanne (författare)
- MedImmune Limited, Cambridge
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(creator_code:org_t)
- 2018-02-20
- 2018
- Engelska.
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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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
- Interleukin (IL)-33 is an IL-1 family alarmin released from damaged epithelial and endothelial barriers to elicit immune responses and allergic inflammation via its receptor ST2. Serine proteases released from neutrophils, mast cells and cytotoxic lymphocytes have been proposed to process the N-terminus of IL-33 to enhance its activity. Here we report that processing of full length IL-33 can occur in mice deficient in these immune cell protease activities. We sought alternative mechanisms for the proteolytic activation of IL-33 and discovered that exogenous allergen proteases and endogenous calpains, from damaged airway epithelial cells, can process full length IL-33 and increase its alarmin activity up to ~60-fold. Processed forms of IL-33 of apparent molecular weights ~18, 20, 22 and 23 kDa, were detected in human lungs consistent with some, but not all, proposed processing sites. Furthermore, allergen proteases degraded processed forms of IL-33 after cysteine residue oxidation. We suggest that IL-33 can sense the proteolytic and oxidative microenvironment during tissue injury that facilitate its rapid activation and inactivation to regulate the duration of its alarmin function.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Scott, Ian C.
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Majithiya, Jayes ...
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Sanden, Caroline
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Thornton, Peter
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Sanders, Philip ...
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Moore, Tom
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visa fler...
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Guscott, Molly
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Corkill, Dominic ...
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Erjefält, Jonas ...
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Cohen, E. Suzann ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Lungmedicin och ...
- Artiklar i publikationen
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Scientific Repor ...
- Av lärosätet
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Lunds universitet