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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Scientific reports 2020-02, Vol.10 (1), p.2886-2886, Article 2886
Hauptverfasser: Żyżyńska-Granica, Barbara, Trzaskowski, Bartosz, Dutkiewicz, Małgorzata, Zegrocka-Stendel, Oliwia, Machcińska, Maja, Bocian, Katarzyna, Kowalewska, Magdalena, Koziak, Katarzyna
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2886
container_issue 1
container_start_page 2886
container_title Scientific reports
container_volume 10
creator Żyżyńska-Granica, Barbara
Trzaskowski, Bartosz
Dutkiewicz, Małgorzata
Zegrocka-Stendel, Oliwia
Machcińska, Maja
Bocian, Katarzyna
Kowalewska, Magdalena
Koziak, Katarzyna
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.
doi_str_mv 10.1038/s41598-020-59798-3
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7031511</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2358526267</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-4a926c403b296c450801b0501070f8fb1779e3e58512c39ad3acae0c04018b523</originalsourceid><addsrcrecordid>eNp9kU1LAzEQhoMoKtU_4EECXrysTr6azUUQ8QsEL3oO2Zhto7tJTbZC_fWm1u-Ducxk5pk3E16E9ggcEWD1ceZEqLoCCpVQsmRsDW1T4KKijNL1H_kW2s35EcoRVHGiNtEWoyDH5bqN7u-mDpsw-MqHtjN9b4aYFngWB1eKpsOxxda15jV2PmCTsY19HwOeLFFsp6ZU7WKITz447MPUN74I7KCN1nTZ7X7EEbq_OL87u6pubi-vz05vKsslHypuFB1bDqyhqkQBNZAGBBCQ0NZtQ6RUjjlRC0ItU-aBGWscWOBA6kZQNkInK93ZvOndgy07J9PpWfK9SQsdjde_O8FP9SS-aAmMCEKKwOGHQIrPc5cH3ftsXdeZ4OI8a8qEYkoKygt68Ad9jPMUyveWVC3omI5loeiKsinmnFz7tQwBvTROr4zTxTj9bpxmZWj_5ze-Rj5tKgBbAbm0wsSl77f_kX0Dqkajew</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2358526267</pqid></control><display><type>article</type><title>The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Free E-Journal (出版社公開部分のみ)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Żyżyńska-Granica, Barbara ; Trzaskowski, Bartosz ; Dutkiewicz, Małgorzata ; Zegrocka-Stendel, Oliwia ; Machcińska, Maja ; Bocian, Katarzyna ; Kowalewska, Magdalena ; Koziak, Katarzyna</creator><creatorcontrib>Żyżyńska-Granica, Barbara ; Trzaskowski, Bartosz ; Dutkiewicz, Małgorzata ; Zegrocka-Stendel, Oliwia ; Machcińska, Maja ; Bocian, Katarzyna ; Kowalewska, Magdalena ; Koziak, Katarzyna</creatorcontrib><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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-59798-3</identifier><identifier>PMID: 32076052</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/21 ; 14 ; 38 ; 42 ; 631/154/433 ; 692/699/249/2510/1758 ; 96 ; 96/106 ; Adult ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; Antibiotics ; Autoimmune diseases ; Binding Sites ; CD11c antigen ; CD11c Antigen - metabolism ; Cefazolin ; Cefazolin - chemistry ; Cefazolin - pharmacology ; Cell proliferation ; Cell Proliferation - drug effects ; Cytokines ; Dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - metabolism ; Humanities and Social Sciences ; Humans ; Interferon-gamma - metabolism ; Interleukin 15 ; Interleukin 17 ; Interleukin 2 ; Interleukin 21 ; Interleukin 4 ; Interleukin 7 ; Interleukin 9 ; Interleukin Receptor Common gamma Subunit - antagonists &amp; inhibitors ; Interleukin Receptor Common gamma Subunit - chemistry ; Interleukin Receptor Common gamma Subunit - metabolism ; Interleukin-15 - metabolism ; Interleukin-2 - metabolism ; Janus Kinase 3 - metabolism ; Leukocytes (mononuclear) ; Male ; Monocytes ; Monocytes - pathology ; multidisciplinary ; Natural killer cells ; Peripheral blood mononuclear cells ; Phosphorylation ; Phosphorylation - drug effects ; Science ; Science (multidisciplinary) ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor necrosis factor-α ; γ-Interferon</subject><ispartof>Scientific reports, 2020-02, Vol.10 (1), p.2886-2886, Article 2886</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-4a926c403b296c450801b0501070f8fb1779e3e58512c39ad3acae0c04018b523</citedby><cites>FETCH-LOGICAL-c474t-4a926c403b296c450801b0501070f8fb1779e3e58512c39ad3acae0c04018b523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031511/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031511/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32076052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Żyżyńska-Granica, Barbara</creatorcontrib><creatorcontrib>Trzaskowski, Bartosz</creatorcontrib><creatorcontrib>Dutkiewicz, Małgorzata</creatorcontrib><creatorcontrib>Zegrocka-Stendel, Oliwia</creatorcontrib><creatorcontrib>Machcińska, Maja</creatorcontrib><creatorcontrib>Bocian, Katarzyna</creatorcontrib><creatorcontrib>Kowalewska, Magdalena</creatorcontrib><creatorcontrib>Koziak, Katarzyna</creatorcontrib><title>The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><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.</description><subject>13/21</subject><subject>14</subject><subject>38</subject><subject>42</subject><subject>631/154/433</subject><subject>692/699/249/2510/1758</subject><subject>96</subject><subject>96/106</subject><subject>Adult</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Autoimmune diseases</subject><subject>Binding Sites</subject><subject>CD11c antigen</subject><subject>CD11c Antigen - metabolism</subject><subject>Cefazolin</subject><subject>Cefazolin - chemistry</subject><subject>Cefazolin - pharmacology</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin 15</subject><subject>Interleukin 17</subject><subject>Interleukin 2</subject><subject>Interleukin 21</subject><subject>Interleukin 4</subject><subject>Interleukin 7</subject><subject>Interleukin 9</subject><subject>Interleukin Receptor Common gamma Subunit - antagonists &amp; inhibitors</subject><subject>Interleukin Receptor Common gamma Subunit - chemistry</subject><subject>Interleukin Receptor Common gamma Subunit - metabolism</subject><subject>Interleukin-15 - metabolism</subject><subject>Interleukin-2 - metabolism</subject><subject>Janus Kinase 3 - metabolism</subject><subject>Leukocytes (mononuclear)</subject><subject>Male</subject><subject>Monocytes</subject><subject>Monocytes - pathology</subject><subject>multidisciplinary</subject><subject>Natural killer cells</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor necrosis factor-α</subject><subject>γ-Interferon</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1LAzEQhoMoKtU_4EECXrysTr6azUUQ8QsEL3oO2Zhto7tJTbZC_fWm1u-Ducxk5pk3E16E9ggcEWD1ceZEqLoCCpVQsmRsDW1T4KKijNL1H_kW2s35EcoRVHGiNtEWoyDH5bqN7u-mDpsw-MqHtjN9b4aYFngWB1eKpsOxxda15jV2PmCTsY19HwOeLFFsp6ZU7WKITz447MPUN74I7KCN1nTZ7X7EEbq_OL87u6pubi-vz05vKsslHypuFB1bDqyhqkQBNZAGBBCQ0NZtQ6RUjjlRC0ItU-aBGWscWOBA6kZQNkInK93ZvOndgy07J9PpWfK9SQsdjde_O8FP9SS-aAmMCEKKwOGHQIrPc5cH3ftsXdeZ4OI8a8qEYkoKygt68Ad9jPMUyveWVC3omI5loeiKsinmnFz7tQwBvTROr4zTxTj9bpxmZWj_5ze-Rj5tKgBbAbm0wsSl77f_kX0Dqkajew</recordid><startdate>20200219</startdate><enddate>20200219</enddate><creator>Żyżyńska-Granica, Barbara</creator><creator>Trzaskowski, Bartosz</creator><creator>Dutkiewicz, Małgorzata</creator><creator>Zegrocka-Stendel, Oliwia</creator><creator>Machcińska, Maja</creator><creator>Bocian, Katarzyna</creator><creator>Kowalewska, Magdalena</creator><creator>Koziak, Katarzyna</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200219</creationdate><title>The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor</title><author>Żyżyńska-Granica, Barbara ; Trzaskowski, Bartosz ; Dutkiewicz, Małgorzata ; Zegrocka-Stendel, Oliwia ; Machcińska, Maja ; Bocian, Katarzyna ; Kowalewska, Magdalena ; Koziak, Katarzyna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-4a926c403b296c450801b0501070f8fb1779e3e58512c39ad3acae0c04018b523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/21</topic><topic>14</topic><topic>38</topic><topic>42</topic><topic>631/154/433</topic><topic>692/699/249/2510/1758</topic><topic>96</topic><topic>96/106</topic><topic>Adult</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Antibiotics</topic><topic>Autoimmune diseases</topic><topic>Binding Sites</topic><topic>CD11c antigen</topic><topic>CD11c Antigen - metabolism</topic><topic>Cefazolin</topic><topic>Cefazolin - chemistry</topic><topic>Cefazolin - pharmacology</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin 15</topic><topic>Interleukin 17</topic><topic>Interleukin 2</topic><topic>Interleukin 21</topic><topic>Interleukin 4</topic><topic>Interleukin 7</topic><topic>Interleukin 9</topic><topic>Interleukin Receptor Common gamma Subunit - antagonists &amp; inhibitors</topic><topic>Interleukin Receptor Common gamma Subunit - chemistry</topic><topic>Interleukin Receptor Common gamma Subunit - metabolism</topic><topic>Interleukin-15 - metabolism</topic><topic>Interleukin-2 - metabolism</topic><topic>Janus Kinase 3 - metabolism</topic><topic>Leukocytes (mononuclear)</topic><topic>Male</topic><topic>Monocytes</topic><topic>Monocytes - pathology</topic><topic>multidisciplinary</topic><topic>Natural killer cells</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor necrosis factor-α</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Żyżyńska-Granica, Barbara</creatorcontrib><creatorcontrib>Trzaskowski, Bartosz</creatorcontrib><creatorcontrib>Dutkiewicz, Małgorzata</creatorcontrib><creatorcontrib>Zegrocka-Stendel, Oliwia</creatorcontrib><creatorcontrib>Machcińska, Maja</creatorcontrib><creatorcontrib>Bocian, Katarzyna</creatorcontrib><creatorcontrib>Kowalewska, Magdalena</creatorcontrib><creatorcontrib>Koziak, Katarzyna</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Żyżyńska-Granica, Barbara</au><au>Trzaskowski, Bartosz</au><au>Dutkiewicz, Małgorzata</au><au>Zegrocka-Stendel, Oliwia</au><au>Machcińska, Maja</au><au>Bocian, Katarzyna</au><au>Kowalewska, Magdalena</au><au>Koziak, Katarzyna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-02-19</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>2886</spage><epage>2886</epage><pages>2886-2886</pages><artnum>2886</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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 (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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32076052</pmid><doi>10.1038/s41598-020-59798-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2045-2322
ispartof Scientific reports, 2020-02, Vol.10 (1), p.2886-2886, Article 2886
issn 2045-2322
2045-2322
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7031511
source MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Free E-Journal (出版社公開部分のみ); PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals
subjects 13/21
14
38
42
631/154/433
692/699/249/2510/1758
96
96/106
Adult
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Antibiotics
Autoimmune diseases
Binding Sites
CD11c antigen
CD11c Antigen - metabolism
Cefazolin
Cefazolin - chemistry
Cefazolin - pharmacology
Cell proliferation
Cell Proliferation - drug effects
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Humanities and Social Sciences
Humans
Interferon-gamma - metabolism
Interleukin 15
Interleukin 17
Interleukin 2
Interleukin 21
Interleukin 4
Interleukin 7
Interleukin 9
Interleukin Receptor Common gamma Subunit - antagonists & inhibitors
Interleukin Receptor Common gamma Subunit - chemistry
Interleukin Receptor Common gamma Subunit - metabolism
Interleukin-15 - metabolism
Interleukin-2 - metabolism
Janus Kinase 3 - metabolism
Leukocytes (mononuclear)
Male
Monocytes
Monocytes - pathology
multidisciplinary
Natural killer cells
Peripheral blood mononuclear cells
Phosphorylation
Phosphorylation - drug effects
Science
Science (multidisciplinary)
Tumor Necrosis Factor-alpha - biosynthesis
Tumor necrosis factor-α
γ-Interferon
title The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T07%3A35%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20anti-inflammatory%20potential%20of%20cefazolin%20as%20common%20gamma%20chain%20cytokine%20inhibitor&rft.jtitle=Scientific%20reports&rft.au=%C5%BBy%C5%BCy%C5%84ska-Granica,%20Barbara&rft.date=2020-02-19&rft.volume=10&rft.issue=1&rft.spage=2886&rft.epage=2886&rft.pages=2886-2886&rft.artnum=2886&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-59798-3&rft_dat=%3Cproquest_pubme%3E2358526267%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2358526267&rft_id=info:pmid/32076052&rfr_iscdi=true