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The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor
A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031511/ https://www.ncbi.nlm.nih.gov/pubmed/32076052 http://dx.doi.org/10.1038/s41598-020-59798-3 |
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author | Żyżyńska-Granica, Barbara Trzaskowski, Bartosz Dutkiewicz, Małgorzata Zegrocka-Stendel, Oliwia Machcińska, Maja Bocian, Katarzyna Kowalewska, Magdalena Koziak, Katarzyna |
author_facet | Żyżyńska-Granica, Barbara Trzaskowski, Bartosz Dutkiewicz, Małgorzata Zegrocka-Stendel, Oliwia Machcińska, Maja Bocian, Katarzyna Kowalewska, Magdalena Koziak, Katarzyna |
author_sort | Żyżyńska-Granica, Barbara |
collection | PubMed |
description | A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γ(c)). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γ(c) subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2- and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γ(c) receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. |
format | Online Article Text |
id | pubmed-7031511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70315112020-02-27 The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor Żyżyńska-Granica, Barbara Trzaskowski, Bartosz Dutkiewicz, Małgorzata Zegrocka-Stendel, Oliwia Machcińska, Maja Bocian, Katarzyna Kowalewska, Magdalena Koziak, Katarzyna Sci Rep Article A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γ(c)). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γ(c) subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2- and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γ(c) receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. Nature Publishing Group UK 2020-02-19 /pmc/articles/PMC7031511/ /pubmed/32076052 http://dx.doi.org/10.1038/s41598-020-59798-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Żyżyńska-Granica, Barbara Trzaskowski, Bartosz Dutkiewicz, Małgorzata Zegrocka-Stendel, Oliwia Machcińska, Maja Bocian, Katarzyna Kowalewska, Magdalena Koziak, Katarzyna The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title | The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title_full | The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title_fullStr | The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title_full_unstemmed | The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title_short | The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
title_sort | anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031511/ https://www.ncbi.nlm.nih.gov/pubmed/32076052 http://dx.doi.org/10.1038/s41598-020-59798-3 |
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