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IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis
Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory re...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768062/ https://www.ncbi.nlm.nih.gov/pubmed/27042303 http://dx.doi.org/10.1002/iid3.95 |
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author | Waern, Ida Karlsson, Iulia Pejler, Gunnar Wernersson, Sara |
author_facet | Waern, Ida Karlsson, Iulia Pejler, Gunnar Wernersson, Sara |
author_sort | Waern, Ida |
collection | PubMed |
description | Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory reaction, either through direct effects of serglycin proteoglycan or through effects mediated by its bound proteases. The objective of this study was to address this scenario by investigating the possibility that serglycin‐associated proteases can regulate levels of pro‐inflammatory cytokines. Indeed, we show here that activated cultured peritoneal mast cells from wild type mice efficiently reduced the levels of exogenously administered IL‐6 and IL‐17A, whereas serglycin‐deficient mast cells lacked this ability. Furthermore, our data suggest that the reduction of IL‐6 and IL‐17A concentrations is due to proteolytic degradation mediated by serglycin‐dependent serine proteases. Moreover, we show that activated mast cells have the capacity to release IL‐6 and that the levels of this cytokine in supernatants were markedly higher in cultures of serglycin‐deficient versus serglycin‐sufficient mast cells, suggesting that serglycin‐dependent serine proteases also participate in the regulation of endogenously produced IL‐6. In summary, although the general consensus is that mast cells have a pathogenic impact on inflammatory settings, this study identifies a role for a mast cell‐derived serglycin:serine protease axis in down‐regulating levels of major inflammatory cytokines. These findings support the notion that mast cells could have a dual role in inflammatory settings, by both being able to secrete pathogenic compounds and being able to regulate their levels after release. |
format | Online Article Text |
id | pubmed-4768062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47680622016-04-01 IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis Waern, Ida Karlsson, Iulia Pejler, Gunnar Wernersson, Sara Immun Inflamm Dis Original Research Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory reaction, either through direct effects of serglycin proteoglycan or through effects mediated by its bound proteases. The objective of this study was to address this scenario by investigating the possibility that serglycin‐associated proteases can regulate levels of pro‐inflammatory cytokines. Indeed, we show here that activated cultured peritoneal mast cells from wild type mice efficiently reduced the levels of exogenously administered IL‐6 and IL‐17A, whereas serglycin‐deficient mast cells lacked this ability. Furthermore, our data suggest that the reduction of IL‐6 and IL‐17A concentrations is due to proteolytic degradation mediated by serglycin‐dependent serine proteases. Moreover, we show that activated mast cells have the capacity to release IL‐6 and that the levels of this cytokine in supernatants were markedly higher in cultures of serglycin‐deficient versus serglycin‐sufficient mast cells, suggesting that serglycin‐dependent serine proteases also participate in the regulation of endogenously produced IL‐6. In summary, although the general consensus is that mast cells have a pathogenic impact on inflammatory settings, this study identifies a role for a mast cell‐derived serglycin:serine protease axis in down‐regulating levels of major inflammatory cytokines. These findings support the notion that mast cells could have a dual role in inflammatory settings, by both being able to secrete pathogenic compounds and being able to regulate their levels after release. John Wiley and Sons Inc. 2015-12-02 /pmc/articles/PMC4768062/ /pubmed/27042303 http://dx.doi.org/10.1002/iid3.95 Text en © 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Waern, Ida Karlsson, Iulia Pejler, Gunnar Wernersson, Sara IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title | IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title_full | IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title_fullStr | IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title_full_unstemmed | IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title_short | IL‐6 and IL‐17A degradation by mast cells is mediated by a serglycin:serine protease axis |
title_sort | il‐6 and il‐17a degradation by mast cells is mediated by a serglycin:serine protease axis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768062/ https://www.ncbi.nlm.nih.gov/pubmed/27042303 http://dx.doi.org/10.1002/iid3.95 |
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