Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking
Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activit...
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| Veröffentlicht in: | Biomedicine & pharmacotherapy 2019-10, Vol.118, p.109152-109152, Article 109152 |
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| creator | Veloso Júnior, Paulo Henrique de Holanda Simon, Karina Smidt de Castro, Raffael Júnio Araújo Coelho, Luísa Coutinho Erazo, Fabián Andres Hurtado de Souza, Adolfo Carlos Barros das Neves, Rogério Coutinho Lozano, Viviane Furlan Schwartz, Elizabeth Ferroni Tavares, Aldo Henrique Mortari, Márcia Renata Junqueira-Kipnis, Ana Paula Silva-Pereira, Ildinete Bocca, Anamelia Lorenzetti |
| description | Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1β transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies. |
| doi_str_mv | 10.1016/j.biopha.2019.109152 |
| format | Article |
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In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1β transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies.</description><identifier>ISSN: 0753-3322</identifier><identifier>EISSN: 1950-6007</identifier><identifier>DOI: 10.1016/j.biopha.2019.109152</identifier><identifier>PMID: 31376652</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Animals ; Anti-Infective Agents - isolation & purification ; Anti-Infective Agents - pharmacology ; Anti-inflammatory ; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Cell Line ; Cryptococcus neoformans - drug effects ; Cytokines - metabolism ; Dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Immunity, Innate - drug effects ; Macrophages ; Macrophages, Peritoneal - drug effects ; Macrophages, Peritoneal - immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Microbial Sensitivity Tests ; Mycobacterium abscessus - drug effects ; Peptides - isolation & purification ; Peptides - pharmacology ; Scorpion venom ; Scorpion Venoms - chemistry ; Scorpions ; Tityus Obscurus ; ToAP3 ; ToaP4 ; Toll-Like Receptor 4 - antagonists & inhibitors ; Toll-Like Receptor 4 - genetics</subject><ispartof>Biomedicine & pharmacotherapy, 2019-10, Vol.118, p.109152-109152, Article 109152</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-8966472b881d3948ca87e486ae6f91d06e79a2c643746593efdd93110a891ddb3</citedby><cites>FETCH-LOGICAL-c408t-8966472b881d3948ca87e486ae6f91d06e79a2c643746593efdd93110a891ddb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopha.2019.109152$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31376652$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veloso Júnior, Paulo Henrique de Holanda</creatorcontrib><creatorcontrib>Simon, Karina Smidt</creatorcontrib><creatorcontrib>de Castro, Raffael Júnio Araújo</creatorcontrib><creatorcontrib>Coelho, Luísa Coutinho</creatorcontrib><creatorcontrib>Erazo, Fabián Andres Hurtado</creatorcontrib><creatorcontrib>de Souza, Adolfo Carlos Barros</creatorcontrib><creatorcontrib>das Neves, Rogério Coutinho</creatorcontrib><creatorcontrib>Lozano, Viviane Furlan</creatorcontrib><creatorcontrib>Schwartz, Elizabeth Ferroni</creatorcontrib><creatorcontrib>Tavares, Aldo Henrique</creatorcontrib><creatorcontrib>Mortari, Márcia Renata</creatorcontrib><creatorcontrib>Junqueira-Kipnis, Ana Paula</creatorcontrib><creatorcontrib>Silva-Pereira, Ildinete</creatorcontrib><creatorcontrib>Bocca, Anamelia Lorenzetti</creatorcontrib><title>Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking</title><title>Biomedicine & pharmacotherapy</title><addtitle>Biomed Pharmacother</addtitle><description>Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1β transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies.</description><subject>Animals</subject><subject>Anti-Infective Agents - isolation & purification</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Anti-inflammatory</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - isolation & purification</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Cell Line</subject><subject>Cryptococcus neoformans - drug effects</subject><subject>Cytokines - metabolism</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Immunity, Innate - drug effects</subject><subject>Macrophages</subject><subject>Macrophages, Peritoneal - drug effects</subject><subject>Macrophages, Peritoneal - immunology</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microbial Sensitivity Tests</subject><subject>Mycobacterium abscessus - drug effects</subject><subject>Peptides - isolation & purification</subject><subject>Peptides - pharmacology</subject><subject>Scorpion venom</subject><subject>Scorpion Venoms - chemistry</subject><subject>Scorpions</subject><subject>Tityus Obscurus</subject><subject>ToAP3</subject><subject>ToaP4</subject><subject>Toll-Like Receptor 4 - antagonists & inhibitors</subject><subject>Toll-Like Receptor 4 - genetics</subject><issn>0753-3322</issn><issn>1950-6007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVJaVy3_6CEPeayrr5WH5dCMEkaMNQU55KL0EqzsdzdlSutA_733XidHHuaYeZ952UehL4RvCCYiO-7RR3ifmsXFBM9jjSp6Ac0I7rCpcBYXqAZlhUrGaP0En3OeYcxrgRTn9AlI0wKUdEZelrDfggecrGJN2tW2N6fOl54cAlshiJBe6qxKULftLbr7BDTsXDHIf4J_WgdtikenrfFZvW75EXdRjfOn7-gj41tM3w91zl6vLvdLH-Wq1_3D8ubVek4VkOptBBc0lop4pnmylklgSthQTSaeCxAakud4ExyUWkGjfeaEYKtGte-ZnN0Pd3dp_j3AHkwXcgO2tb2EA_ZUCoUw1IwOUr5JHUp5pygMfsUOpuOhmDzStXszETVvFI1E9XRdnVOONQd-HfTG8ZR8GMSwPjnS4BksgvQO_AhgRuMj-H_Cf8A5PeIog</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Veloso Júnior, Paulo Henrique de Holanda</creator><creator>Simon, Karina Smidt</creator><creator>de Castro, Raffael Júnio Araújo</creator><creator>Coelho, Luísa Coutinho</creator><creator>Erazo, Fabián Andres Hurtado</creator><creator>de Souza, Adolfo Carlos Barros</creator><creator>das Neves, Rogério Coutinho</creator><creator>Lozano, Viviane Furlan</creator><creator>Schwartz, Elizabeth Ferroni</creator><creator>Tavares, Aldo Henrique</creator><creator>Mortari, Márcia Renata</creator><creator>Junqueira-Kipnis, Ana Paula</creator><creator>Silva-Pereira, Ildinete</creator><creator>Bocca, Anamelia Lorenzetti</creator><general>Elsevier Masson SAS</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>201910</creationdate><title>Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking</title><author>Veloso Júnior, Paulo Henrique de Holanda ; Simon, Karina Smidt ; de Castro, Raffael Júnio Araújo ; Coelho, Luísa Coutinho ; Erazo, Fabián Andres Hurtado ; de Souza, Adolfo Carlos Barros ; das Neves, Rogério Coutinho ; Lozano, Viviane Furlan ; Schwartz, Elizabeth Ferroni ; Tavares, Aldo Henrique ; Mortari, Márcia Renata ; Junqueira-Kipnis, Ana Paula ; Silva-Pereira, Ildinete ; Bocca, Anamelia Lorenzetti</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-8966472b881d3948ca87e486ae6f91d06e79a2c643746593efdd93110a891ddb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Anti-Infective Agents - isolation & purification</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Anti-inflammatory</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - isolation & purification</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Cell Line</topic><topic>Cryptococcus neoformans - drug effects</topic><topic>Cytokines - metabolism</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Immunity, Innate - drug effects</topic><topic>Macrophages</topic><topic>Macrophages, Peritoneal - drug effects</topic><topic>Macrophages, Peritoneal - immunology</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microbial Sensitivity Tests</topic><topic>Mycobacterium abscessus - drug effects</topic><topic>Peptides - isolation & purification</topic><topic>Peptides - pharmacology</topic><topic>Scorpion venom</topic><topic>Scorpion Venoms - chemistry</topic><topic>Scorpions</topic><topic>Tityus Obscurus</topic><topic>ToAP3</topic><topic>ToaP4</topic><topic>Toll-Like Receptor 4 - antagonists & inhibitors</topic><topic>Toll-Like Receptor 4 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Veloso Júnior, Paulo Henrique de Holanda</creatorcontrib><creatorcontrib>Simon, Karina Smidt</creatorcontrib><creatorcontrib>de Castro, Raffael Júnio Araújo</creatorcontrib><creatorcontrib>Coelho, Luísa Coutinho</creatorcontrib><creatorcontrib>Erazo, Fabián Andres Hurtado</creatorcontrib><creatorcontrib>de Souza, Adolfo Carlos Barros</creatorcontrib><creatorcontrib>das Neves, Rogério Coutinho</creatorcontrib><creatorcontrib>Lozano, Viviane Furlan</creatorcontrib><creatorcontrib>Schwartz, Elizabeth Ferroni</creatorcontrib><creatorcontrib>Tavares, Aldo Henrique</creatorcontrib><creatorcontrib>Mortari, Márcia Renata</creatorcontrib><creatorcontrib>Junqueira-Kipnis, Ana Paula</creatorcontrib><creatorcontrib>Silva-Pereira, Ildinete</creatorcontrib><creatorcontrib>Bocca, Anamelia Lorenzetti</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Biomedicine & pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Veloso Júnior, Paulo Henrique de Holanda</au><au>Simon, Karina Smidt</au><au>de Castro, Raffael Júnio Araújo</au><au>Coelho, Luísa Coutinho</au><au>Erazo, Fabián Andres Hurtado</au><au>de Souza, Adolfo Carlos Barros</au><au>das Neves, Rogério Coutinho</au><au>Lozano, Viviane Furlan</au><au>Schwartz, Elizabeth Ferroni</au><au>Tavares, Aldo Henrique</au><au>Mortari, Márcia Renata</au><au>Junqueira-Kipnis, Ana Paula</au><au>Silva-Pereira, Ildinete</au><au>Bocca, Anamelia Lorenzetti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking</atitle><jtitle>Biomedicine & pharmacotherapy</jtitle><addtitle>Biomed Pharmacother</addtitle><date>2019-10</date><risdate>2019</risdate><volume>118</volume><spage>109152</spage><epage>109152</epage><pages>109152-109152</pages><artnum>109152</artnum><issn>0753-3322</issn><eissn>1950-6007</eissn><abstract>Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1β transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>31376652</pmid><doi>10.1016/j.biopha.2019.109152</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biomedicine & pharmacotherapy, 2019-10, Vol.118, p.109152-109152, Article 109152 |
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| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Anti-Infective Agents - isolation & purification Anti-Infective Agents - pharmacology Anti-inflammatory Anti-Inflammatory Agents, Non-Steroidal - isolation & purification Anti-Inflammatory Agents, Non-Steroidal - pharmacology Cell Line Cryptococcus neoformans - drug effects Cytokines - metabolism Dendritic cells Dendritic Cells - drug effects Dendritic Cells - immunology Immunity, Innate - drug effects Macrophages Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - immunology Mice, Inbred C57BL Mice, Knockout Microbial Sensitivity Tests Mycobacterium abscessus - drug effects Peptides - isolation & purification Peptides - pharmacology Scorpion venom Scorpion Venoms - chemistry Scorpions Tityus Obscurus ToAP3 ToaP4 Toll-Like Receptor 4 - antagonists & inhibitors Toll-Like Receptor 4 - genetics |
| title | Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking |
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