2. Academic Validation
  3. The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor

The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor

  • Sci Rep. 2020 Feb 19;10(1):2886. doi: 10.1038/s41598-020-59798-3.
Barbara Żyżyńska-Granica 1 2,  Bartosz Trzaskowski 3,  Małgorzata Dutkiewicz 4,  Oliwia Zegrocka-Stendel 4,  Maja Machcińska 5 6,  Katarzyna Bocian 6,  Magdalena Kowalewska 4 7,  Katarzyna Koziak 8
Affiliations

Affiliations

  • 1 Department of Pharmacodynamics, Centre for Preclinical Research and Technologies, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland.
  • 2 Chair and Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097, Warsaw, Poland.
  • 3 University of Warsaw, Centre of New Technologies, Banacha 2c, 02-097, Warsaw, Poland.
  • 4 Department of Immunology, Biochemistry and Nutrition, Centre for Preclinical Research and Technologies, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland.
  • 5 Laboratory of Parasitology, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland.
  • 6 Department of Immunology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096, Warsaw, Poland.
  • 7 Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Centre, Roentgena 5, 02-781, Warsaw, Poland.
  • 8 Department of Immunology, Biochemistry and Nutrition, Centre for Preclinical Research and Technologies, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland. katarzyna.koziak@wum.edu.pl.
PMID: 32076052 DOI: 10.1038/s41598-020-59798-3
Abstract

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 (γc). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γc 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 γc receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

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