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Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis

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
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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
Title:Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
Series/Journal:Biological chemistry (1437-4315)
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:
Type of IDID
Web of Science (WoS)000311051400017
DOI10.1515/hsz-2012-0189
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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