Waern, Ida and Karlsson, Iulia and Schlenner, SM and Feyerabend, TB and Rodewald, HR and Åbrink, Magnus and Hellman, L and Pejler, Gunnar and Wernersson, Sara
(2012).
Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis.
Biological chemistry. 393
:12
, 1555-1567
[Journal article]
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844kB |
Official URL: http://dx.doi.org/10.1515/hsz-2012-0189
Abstract
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.
Authors/Creators: | Waern, Ida and Karlsson, Iulia and Schlenner, SM and Feyerabend, TB and Rodewald, HR and Åbrink, Magnus and Hellman, L and Pejler, Gunnar and Wernersson, Sara | ||||||
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Title: | Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis | ||||||
Series Name/Journal: | Biological chemistry | ||||||
Year of publishing : | 12 November 2012 | ||||||
Volume: | 393 | ||||||
Number: | 12 | ||||||
Page range: | 1555-1567 | ||||||
Number of Pages: | 13 | ||||||
Publisher: | De Gruyter Open Library | ||||||
ISSN: | 1437-4315 | ||||||
Language: | English | ||||||
Additional Information: | Published in accordance with the publishing policy of De Gruyter Open Library | ||||||
Publication Type: | Journal article | ||||||
Refereed: | Yes | ||||||
Article category: | Scientific peer reviewed | ||||||
Version: | Published version | ||||||
Full Text Status: | Public | ||||||
Agris subject categories.: | L Animal production > L50 Animal physiology and biochemistry X Agricola extesions > X30 Life sciences | ||||||
Subjects: | (A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology (A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience | ||||||
Keywords: | allergy, cytokine, mast cell, proteoglycan, serine protease | ||||||
URN:NBN: | urn:nbn:se:slu:epsilon-e-1650 | ||||||
Permanent URL: | http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-1650 | ||||||
Additional ID: |
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ID Code: | 10836 | ||||||
Department: | (VH) > Dept. of Anatomy, Physiology and Biochemistry (VH) > Dept. of Biomedical Sciences and Veterinary Public Health | ||||||
Deposited By: | SLUpub Connector | ||||||
Deposited On: | 04 Oct 2013 08:33 | ||||||
Metadata Last Modified: | 26 Dec 2014 00:44 |
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