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Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice
•Tetrathiomolybdate (TM) inhibited imiquimod-induced psoriasiform lesions in mice.•TM decreased cytokine levels in inflamed skin, splenocyte, and draining lymph node.•TM inhibited signals activation (Erk1/2 and STAT3) in keratinocyte and splenocyte. Copper is an essential metal for maintenance of ma...
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Published in: | Journal of dermatological science 2018-10, Vol.92 (1), p.30-37 |
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creator | Hsu, Peng-Yang Yen, Hsu-Heng Yang, Tao-Hsiang Su, Che-Chun |
description | •Tetrathiomolybdate (TM) inhibited imiquimod-induced psoriasiform lesions in mice.•TM decreased cytokine levels in inflamed skin, splenocyte, and draining lymph node.•TM inhibited signals activation (Erk1/2 and STAT3) in keratinocyte and splenocyte.
Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson’s disease, and decreased the severity of autoimmune arthritis in mice.
In this report, we evaluated the effects of TM in a mouse model for psoriasis.
Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors.
Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3.
These findings are strong evidence that TM can inhibit psoriasis in the model. |
doi_str_mv | 10.1016/j.jdermsci.2018.08.003 |
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Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson’s disease, and decreased the severity of autoimmune arthritis in mice.
In this report, we evaluated the effects of TM in a mouse model for psoriasis.
Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors.
Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3.
These findings are strong evidence that TM can inhibit psoriasis in the model.</description><identifier>ISSN: 0923-1811</identifier><identifier>EISSN: 1873-569X</identifier><identifier>DOI: 10.1016/j.jdermsci.2018.08.003</identifier><identifier>PMID: 30126748</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Chelating Agents - pharmacology ; Copper ; Copper - metabolism ; Cytokines - metabolism ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Imiquimod ; Inflammation Mediators - metabolism ; Keratinocytes - drug effects ; Keratinocytes - immunology ; Keratinocytes - metabolism ; Male ; Mice, Inbred C57BL ; Molybdenum - pharmacology ; Phosphorylation ; Psoriasis ; Psoriasis - chemically induced ; Psoriasis - immunology ; Psoriasis - metabolism ; Psoriasis - prevention & control ; Signal Transduction - drug effects ; Skin - drug effects ; Skin - immunology ; Skin - metabolism ; Skin - pathology ; Spleen - drug effects ; Spleen - immunology ; Spleen - metabolism ; STAT3 Transcription Factor - metabolism ; Tetrathiomolybdate</subject><ispartof>Journal of dermatological science, 2018-10, Vol.92 (1), p.30-37</ispartof><rights>2018 Japanese Society for Investigative Dermatology</rights><rights>Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-620d2612aaa8c46356140e6c96d398f07557b0f758025c064213b0c9f3149b653</citedby><cites>FETCH-LOGICAL-c440t-620d2612aaa8c46356140e6c96d398f07557b0f758025c064213b0c9f3149b653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30126748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Peng-Yang</creatorcontrib><creatorcontrib>Yen, Hsu-Heng</creatorcontrib><creatorcontrib>Yang, Tao-Hsiang</creatorcontrib><creatorcontrib>Su, Che-Chun</creatorcontrib><title>Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice</title><title>Journal of dermatological science</title><addtitle>J Dermatol Sci</addtitle><description>•Tetrathiomolybdate (TM) inhibited imiquimod-induced psoriasiform lesions in mice.•TM decreased cytokine levels in inflamed skin, splenocyte, and draining lymph node.•TM inhibited signals activation (Erk1/2 and STAT3) in keratinocyte and splenocyte.
Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson’s disease, and decreased the severity of autoimmune arthritis in mice.
In this report, we evaluated the effects of TM in a mouse model for psoriasis.
Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors.
Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3.
These findings are strong evidence that TM can inhibit psoriasis in the model.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Chelating Agents - pharmacology</subject><subject>Copper</subject><subject>Copper - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Imiquimod</subject><subject>Inflammation Mediators - metabolism</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - immunology</subject><subject>Keratinocytes - metabolism</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Molybdenum - pharmacology</subject><subject>Phosphorylation</subject><subject>Psoriasis</subject><subject>Psoriasis - chemically induced</subject><subject>Psoriasis - immunology</subject><subject>Psoriasis - metabolism</subject><subject>Psoriasis - prevention & control</subject><subject>Signal Transduction - drug effects</subject><subject>Skin - drug effects</subject><subject>Skin - immunology</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Spleen - drug effects</subject><subject>Spleen - immunology</subject><subject>Spleen - metabolism</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Tetrathiomolybdate</subject><issn>0923-1811</issn><issn>1873-569X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkEtr3DAQgEVISTZp_0LwMYd6M3pYtm8NoXlAIJcUCj0IWRqz2lrWRpID-ffVskmvgYFhhm9mmI-QCwprClRebddbi9En49YMaLeGEsCPyIp2La8b2f8-JivoGa9pR-kpOUtpCwANE_0JOeVAmWxFtyJ_njFHnTcu-DC9DVZn_F7pyoTdDmNlNjjpHGLl5o0bXEZbOe9eFueDrd1sF1M66a-bCzBO2nudXdgXlXcGv5Ivo54SfnvP5-TX7c_nm_v68enu4eb6sTZCQK4lA8skZVrrzgjJG0kFoDS9tLzvRmibph1gbJsOWGNACkb5AKYfORX9IBt-Ti4Pe3cxvCyYsvIuGZwmPWNYkmLQUyZAcFlQeUBNDClFHNUuOq_jm6Kg9mLVVn2IVXuxCkoAL4MX7zeWwaP9P_ZhsgA_DgCWT18dRlVW4FwEuYgmKxvcZzf-AbCLjQE</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Hsu, Peng-Yang</creator><creator>Yen, Hsu-Heng</creator><creator>Yang, Tao-Hsiang</creator><creator>Su, Che-Chun</creator><general>Elsevier B.V</general><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>7X8</scope></search><sort><creationdate>201810</creationdate><title>Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice</title><author>Hsu, Peng-Yang ; Yen, Hsu-Heng ; Yang, Tao-Hsiang ; Su, Che-Chun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-620d2612aaa8c46356140e6c96d398f07557b0f758025c064213b0c9f3149b653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Chelating Agents - pharmacology</topic><topic>Copper</topic><topic>Copper - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Imiquimod</topic><topic>Inflammation Mediators - metabolism</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - immunology</topic><topic>Keratinocytes - metabolism</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Molybdenum - pharmacology</topic><topic>Phosphorylation</topic><topic>Psoriasis</topic><topic>Psoriasis - chemically induced</topic><topic>Psoriasis - immunology</topic><topic>Psoriasis - metabolism</topic><topic>Psoriasis - prevention & control</topic><topic>Signal Transduction - drug effects</topic><topic>Skin - drug effects</topic><topic>Skin - immunology</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Spleen - drug effects</topic><topic>Spleen - immunology</topic><topic>Spleen - metabolism</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Tetrathiomolybdate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, Peng-Yang</creatorcontrib><creatorcontrib>Yen, Hsu-Heng</creatorcontrib><creatorcontrib>Yang, Tao-Hsiang</creatorcontrib><creatorcontrib>Su, Che-Chun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of dermatological science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, Peng-Yang</au><au>Yen, Hsu-Heng</au><au>Yang, Tao-Hsiang</au><au>Su, Che-Chun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice</atitle><jtitle>Journal of dermatological science</jtitle><addtitle>J Dermatol Sci</addtitle><date>2018-10</date><risdate>2018</risdate><volume>92</volume><issue>1</issue><spage>30</spage><epage>37</epage><pages>30-37</pages><issn>0923-1811</issn><eissn>1873-569X</eissn><abstract>•Tetrathiomolybdate (TM) inhibited imiquimod-induced psoriasiform lesions in mice.•TM decreased cytokine levels in inflamed skin, splenocyte, and draining lymph node.•TM inhibited signals activation (Erk1/2 and STAT3) in keratinocyte and splenocyte.
Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson’s disease, and decreased the severity of autoimmune arthritis in mice.
In this report, we evaluated the effects of TM in a mouse model for psoriasis.
Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors.
Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3.
These findings are strong evidence that TM can inhibit psoriasis in the model.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30126748</pmid><doi>10.1016/j.jdermsci.2018.08.003</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anti-Inflammatory Agents - pharmacology Chelating Agents - pharmacology Copper Copper - metabolism Cytokines - metabolism Disease Models, Animal Extracellular Signal-Regulated MAP Kinases - metabolism Imiquimod Inflammation Mediators - metabolism Keratinocytes - drug effects Keratinocytes - immunology Keratinocytes - metabolism Male Mice, Inbred C57BL Molybdenum - pharmacology Phosphorylation Psoriasis Psoriasis - chemically induced Psoriasis - immunology Psoriasis - metabolism Psoriasis - prevention & control Signal Transduction - drug effects Skin - drug effects Skin - immunology Skin - metabolism Skin - pathology Spleen - drug effects Spleen - immunology Spleen - metabolism STAT3 Transcription Factor - metabolism Tetrathiomolybdate |
title | Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice |
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