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Research article - Peer-reviewed, 2012

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

Waern, Ida; Karlsson, Iulia; Schlenner, SM; Feyerabend, TB; Rodewald, HR; Åbrink, Magnus; Hellman, L; Pejler, Gunnar; Wernersson, Sara

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.

Keywords

allergy; cytokine; mast cell; proteoglycan; serine protease

Published in

Biological Chemistry
2012, volume: 393, number: 12, pages: 1555-1567
Publisher: WALTER DE GRUYTER & CO GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY

Authors' information

Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Karlsson, Iulia
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Schlenner, SM
Feyerabend, TB
Rodewald, HR
Hellman, L
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)

UKÄ Subject classification

Cell and Molecular Biology
Medical Bioscience

Publication Identifiers

DOI: https://doi.org/10.1515/hsz-2012-0189

URI (permanent link to this page)

https://res.slu.se/id/publ/38835