Repurposing the anthelmintic praziquantel to treat psoriasis
Background and Purpose The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis. Experimental Approach Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical...
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| Veröffentlicht in: | British journal of pharmacology 2021-12, Vol.178 (23), p.4726-4740 |
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| container_title | British journal of pharmacology |
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| creator | Hao, Lihua Mao, Yuancheng Park, Jin Bae, Eun Ju Park, Byung‐Hyun |
| description | Background and Purpose
The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
Experimental Approach
Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period.
Key Results
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
Conclusion and Implications
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
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| doi_str_mv | 10.1111/bph.15652 |
| format | Article |
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The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
Experimental Approach
Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period.
Key Results
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
Conclusion and Implications
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
▪▪</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.15652</identifier><identifier>PMID: 34363611</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; Anthelmintic agents ; Anthelmintics - adverse effects ; Antiviral drugs ; CD4 antigen ; Cell size ; Disease Models, Animal ; Drug Repositioning ; Flow cytometry ; Helper cells ; IL‐23 ; Imiquimod ; Immune response ; Infiltration ; Inflammation ; Keratinocytes ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Phosphorylation ; Praziquantel ; Praziquantel - pharmacology ; Praziquantel - therapeutic use ; Psoriasis ; Psoriasis - drug therapy ; Psoriasis - metabolism ; Schistosomiasis ; Skin - metabolism ; Spleen ; STAT3 ; Stat3 protein ; Th17 cell ; Th17 Cells ; Topical application</subject><ispartof>British journal of pharmacology, 2021-12, Vol.178 (23), p.4726-4740</ispartof><rights>2021 The British Pharmacological Society</rights><rights>2021 The British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-bb81ac2013cc45ae47822ce59faec10c855d81e876dcf70e17ebc8ae1ae1c30e3</citedby><cites>FETCH-LOGICAL-c3882-bb81ac2013cc45ae47822ce59faec10c855d81e876dcf70e17ebc8ae1ae1c30e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbph.15652$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbph.15652$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34363611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hao, Lihua</creatorcontrib><creatorcontrib>Mao, Yuancheng</creatorcontrib><creatorcontrib>Park, Jin</creatorcontrib><creatorcontrib>Bae, Eun Ju</creatorcontrib><creatorcontrib>Park, Byung‐Hyun</creatorcontrib><title>Repurposing the anthelmintic praziquantel to treat psoriasis</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and Purpose
The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
Experimental Approach
Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period.
Key Results
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
Conclusion and Implications
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
▪▪</description><subject>Animals</subject><subject>Anthelmintic agents</subject><subject>Anthelmintics - adverse effects</subject><subject>Antiviral drugs</subject><subject>CD4 antigen</subject><subject>Cell size</subject><subject>Disease Models, Animal</subject><subject>Drug Repositioning</subject><subject>Flow cytometry</subject><subject>Helper cells</subject><subject>IL‐23</subject><subject>Imiquimod</subject><subject>Immune response</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Keratinocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Phosphorylation</subject><subject>Praziquantel</subject><subject>Praziquantel - pharmacology</subject><subject>Praziquantel - therapeutic use</subject><subject>Psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - metabolism</subject><subject>Schistosomiasis</subject><subject>Skin - metabolism</subject><subject>Spleen</subject><subject>STAT3</subject><subject>Stat3 protein</subject><subject>Th17 cell</subject><subject>Th17 Cells</subject><subject>Topical application</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E9LwzAYBvAgipvTg19ACl700C1v0zQZeNGhThgooueSZm9dRv8taZH56Y12ehAMIS8kPx7CQ8gp0DH4Ncma1Rh4wqM9MoRYJCFnEvbJkFIqQgApB-TIuTWl_lHwQzJgMUtYAjAkV8_YdLapnanegnaFgar8WZSmao0OGqs-zKbzd1gEbR20FlUbNK62RjnjjslBrgqHJ7s5Iq93ty-zebh4vH-YXS9CzaSMwiyToHREgWkdc4WxkFGkkU9zhRqolpwvJaAUyVLngiIIzLRUCH5rRpGNyEWf29h606Fr09I4jUWhKqw7l0acT-NIRBw8Pf9D13VnK_87r6ZciIRNhVeXvdK2ds5injbWlMpuU6DpV6WprzT9rtTbs11il5W4_JU_HXow6cG7KXD7f1J68zTvIz8Bp7iAIw</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Hao, Lihua</creator><creator>Mao, Yuancheng</creator><creator>Park, Jin</creator><creator>Bae, Eun Ju</creator><creator>Park, Byung‐Hyun</creator><general>Blackwell Publishing Ltd</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>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>202112</creationdate><title>Repurposing the anthelmintic praziquantel to treat psoriasis</title><author>Hao, Lihua ; Mao, Yuancheng ; Park, Jin ; Bae, Eun Ju ; Park, Byung‐Hyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3882-bb81ac2013cc45ae47822ce59faec10c855d81e876dcf70e17ebc8ae1ae1c30e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anthelmintic agents</topic><topic>Anthelmintics - adverse effects</topic><topic>Antiviral drugs</topic><topic>CD4 antigen</topic><topic>Cell size</topic><topic>Disease Models, Animal</topic><topic>Drug Repositioning</topic><topic>Flow cytometry</topic><topic>Helper cells</topic><topic>IL‐23</topic><topic>Imiquimod</topic><topic>Immune response</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Keratinocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Phosphorylation</topic><topic>Praziquantel</topic><topic>Praziquantel - pharmacology</topic><topic>Praziquantel - therapeutic use</topic><topic>Psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - metabolism</topic><topic>Schistosomiasis</topic><topic>Skin - metabolism</topic><topic>Spleen</topic><topic>STAT3</topic><topic>Stat3 protein</topic><topic>Th17 cell</topic><topic>Th17 Cells</topic><topic>Topical application</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hao, Lihua</creatorcontrib><creatorcontrib>Mao, Yuancheng</creatorcontrib><creatorcontrib>Park, Jin</creatorcontrib><creatorcontrib>Bae, Eun Ju</creatorcontrib><creatorcontrib>Park, Byung‐Hyun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hao, Lihua</au><au>Mao, Yuancheng</au><au>Park, Jin</au><au>Bae, Eun Ju</au><au>Park, Byung‐Hyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repurposing the anthelmintic praziquantel to treat psoriasis</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2021-12</date><risdate>2021</risdate><volume>178</volume><issue>23</issue><spage>4726</spage><epage>4740</epage><pages>4726-4740</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and Purpose
The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
Experimental Approach
Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period.
Key Results
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
Conclusion and Implications
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
▪▪</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>34363611</pmid><doi>10.1111/bph.15652</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anthelmintic agents Anthelmintics - adverse effects Antiviral drugs CD4 antigen Cell size Disease Models, Animal Drug Repositioning Flow cytometry Helper cells IL‐23 Imiquimod Immune response Infiltration Inflammation Keratinocytes Lymphocytes T Mice Mice, Inbred BALB C Phosphorylation Praziquantel Praziquantel - pharmacology Praziquantel - therapeutic use Psoriasis Psoriasis - drug therapy Psoriasis - metabolism Schistosomiasis Skin - metabolism Spleen STAT3 Stat3 protein Th17 cell Th17 Cells Topical application |
| title | Repurposing the anthelmintic praziquantel to treat psoriasis |
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