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Mast cells limit ex...
Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
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- Waern, Ida (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Institutionen för anatomi, fysiologi och biokemi - afb (slu), avdelningen för biokemi - (slu)
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- Karlsson, Iulia (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Institutionen för anatomi, fysiologi och biokemi - afb (slu), avdelningen för biokemi - (slu)
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- Thorpe, Michael (author)
- Uppsala universitet,Kemisk biologi
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Schlenner, Susan M. (author)
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Feyerabend, Thorsten B. (author)
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Rodewald, Hans-Reimer (author)
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- Åbrink, Magnus (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health
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- Hellman, Lars (author)
- Uppsala universitet,Kemisk biologi
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- Pejler, Gunnar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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- Wernersson, Sara (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Institutionen för anatomi, fysiologi och biokemi - afb (slu), avdelningen för biokemi - (slu)
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(creator_code:org_t)
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- 2012-11-13
- 2012
- English.
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In: Biological chemistry (Print). - : Walter de Gruyter GmbH. - 1431-6730 .- 1437-4315. ; 393:12, s. 1555-1567
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Abstract
Subject headings
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- Mast cell (MC) granules contain large amounts of proteases of the chymase, tryptase and carboxypeptidase A (MC-CPA) type that are stored in complex with serglycin, a proteoglycan with heparin side chains. Hence, serglycin-protease complexes are released upon MC degranulation and may influence local inflammation. Here we explored the possibility that a serglycin-protease axis may regulate levels of IL-13, a cytokine involved in allergic asthma. Indeed, we found that wild-type MCs efficiently degraded exogenous or endogenously produced IL-13 upon degranulation, whereas serglycin(-/-) MCs completely lacked this ability. Moreover, MC-mediated IL-13 degradation was blocked both by a serine protease inhibitor and by a heparin antagonist, which suggests that IL-13 degradation is catalyzed by serglycin-dependent serine proteases and that optimal IL-13 degradation is dependent on both the serglycin and the protease component of the serglycin-protease complex. Moreover, IL-13 degradation was abrogated in MC-CPA(-/-) MC cultures, but was normal in cultures of MCs with an inactivating mutation of MC-CPA, which suggests that the IL-13-degrading serine proteases rely on MC-CPA protein. Together, our data implicate a serglycin-serine protease axis in the regulation of extracellular levels of IL-13. Reduction of IL-13 levels through this mechanism possibly can provide a protective function in the context of allergic inflammation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Medicinsk biovetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Medical Bioscience (hsv//eng)
Keyword
- allergy
- cytokine
- mast cell
- proteoglycan
- serine protease
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Waern, Ida
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Karlsson, Iulia
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Thorpe, Michael
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Schlenner, Susan ...
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Feyerabend, Thor ...
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Rodewald, Hans-R ...
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show more...
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Åbrink, Magnus
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Hellman, Lars
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Pejler, Gunnar
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Wernersson, Sara
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Medical Bioscien ...
- Articles in the publication
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Biological chemi ...
- By the university
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Uppsala University
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Swedish University of Agricultural Sciences