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Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
Institutionen för anatomi, fysiologi och biokemi - afb (slu), avdelningen för biokemi - (slu).
Institutionen för anatomi, fysiologi och biokemi - afb (slu), avdelningen för biokemi - (slu).
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
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2012 (English)In: Biological chemistry (Print), ISSN 1431-6730, E-ISSN 1437-4315, Vol. 393, no 12, 1555-1567 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 393, no 12, 1555-1567 p.
Keyword [en]
allergy, cytokine, mast cell, proteoglycan, serine protease
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-188395DOI: 10.1515/hsz-2012-0189ISI: 000311051400017OAI: oai:DiVA.org:uu-188395DiVA: diva2:578815
Available from: 2012-12-19 Created: 2012-12-17 Last updated: 2017-12-06Bibliographically approved

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Waern, IdaKarlsson, IuliaThorpe, MichaelHellman, LarsWernersson, Sara

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