Title: Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
Authors: Waern, Ida
Karlsson, Iulia
Thorpe, Michael
Schlenner, Susan
Feyerabend, Thorsten B
Rodewald, Hans-Reimer
Abrink, Magnus
Hellman, Lars
Pejler, Gunnar
Wernersson, Sara # ×
Issue Date: Dec-2012
Publisher: W. de Gruyter
Series Title: Biological Chemistry vol:393 issue:12 pages:1555-1567
Article number: 10.1515/hsz-2012-0189
Abstract: Abstract Mast cell (MC) granules contain large amounts of proteases of chymase, tryptase and carboxypeptidase A (MC-CPA) type, 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 WT MCs efficiently degraded exogenous or endogenously produced IL-13 upon degranulation, whereas serglycin-/- MCs totally lacked this ability. Moreover, MCmediated IL-13 degradation was blocked both by a serine protease inhibitor and by a heparin antagonist, suggesting that IL-13 degradation was catalyzed by serglycin-dependent serine proteases and that optimal IL-13 degradation was 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, suggesting 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. Possibly, reduction of IL-13 levels through this mechanism can provide a protective function in the context of allergic inflammation.
ISSN: 1431-6730
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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