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Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo
Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector , is a specific inhibitor of the human coagulation factor Xa (FXa)...
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Published in: | ImmunoHorizons 2022-06, Vol.6 (6), p.373-383 |
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creator | Shrivastava, Gaurav Valenzuela-Leon, Paola Carolina Chagas, Andrezza Campos Kern, Olivia Botello, Karina Zhang, Yixiang Martin-Martin, Ines Oliveira, Markus Berger Tirloni, Lucas Calvo, Eric |
description | Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector
, is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding. |
doi_str_mv | 10.4049/immunohorizons.2200045 |
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, is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding.</description><identifier>ISSN: 2573-7732</identifier><identifier>EISSN: 2573-7732</identifier><identifier>DOI: 10.4049/immunohorizons.2200045</identifier><identifier>PMID: 35738824</identifier><language>eng</language><publisher>United States</publisher><subject>Aedes - metabolism ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anticoagulants - pharmacology ; Cytokines ; Endothelial Cells - metabolism ; Humans ; Interleukin-6 ; Mosquito Vectors ; Receptor, PAR-1 - genetics ; Receptor, PAR-1 - metabolism</subject><ispartof>ImmunoHorizons, 2022-06, Vol.6 (6), p.373-383</ispartof><rights>Copyright © 2022 The Authors.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c282t-f74467b079447227dd1bbef4c2af1d6798a0d830f8fb5bc6c27a1b9b9f5729a23</citedby><cites>FETCH-LOGICAL-c282t-f74467b079447227dd1bbef4c2af1d6798a0d830f8fb5bc6c27a1b9b9f5729a23</cites><orcidid>0000-0001-7670-2584 ; 0000-0002-5740-5178 ; 0000-0003-4582-7100 ; 0000-0003-3229-4106 ; 0000-0001-7880-2730 ; 0000-0003-3577-5423 ; 0000-0002-0956-7324 ; 0000-0003-3422-8436</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35738824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shrivastava, Gaurav</creatorcontrib><creatorcontrib>Valenzuela-Leon, Paola Carolina</creatorcontrib><creatorcontrib>Chagas, Andrezza Campos</creatorcontrib><creatorcontrib>Kern, Olivia</creatorcontrib><creatorcontrib>Botello, Karina</creatorcontrib><creatorcontrib>Zhang, Yixiang</creatorcontrib><creatorcontrib>Martin-Martin, Ines</creatorcontrib><creatorcontrib>Oliveira, Markus Berger</creatorcontrib><creatorcontrib>Tirloni, Lucas</creatorcontrib><creatorcontrib>Calvo, Eric</creatorcontrib><title>Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo</title><title>ImmunoHorizons</title><addtitle>Immunohorizons</addtitle><description>Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector
, is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding.</description><subject>Aedes - metabolism</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anticoagulants - pharmacology</subject><subject>Cytokines</subject><subject>Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Interleukin-6</subject><subject>Mosquito Vectors</subject><subject>Receptor, PAR-1 - genetics</subject><subject>Receptor, PAR-1 - metabolism</subject><issn>2573-7732</issn><issn>2573-7732</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpVkc9OHSEUh0nTphr1FQzLLhzLvxlmVs3EamtiY6PWdEeAgXtpZmAKzE3sK_Sli95boysg5zvfAX4AHGN0yhDrPrppWnxYh-j-BJ9OCUEIsfoN2Cc1pxXnlLx9sd8DRyn9KgjBDHHK3oM9WmptS9g--NuPKiQTZ-dPYF4b-E06D2_l6DYyPsDeZ6eDXC2j9BnaGKYn6LNLRiYD743OIcLeDCZBWUyz03lJ8OSRmEf5kJ4M1cVPWX3vb-CtW_mi9it46eG9yzFA6YftYRMOwTsrx2SOdusB-HFxfnf2tbq6_nJ51l9VmrQkV5Yz1nCFeMcYJ4QPA1bKWKaJtHhoeNdKNLQU2daqWulGEy6x6lRna046SegB-LT1zouazKCNz1GOYo5uKm8WQTrxuuLdWqzCRmDEa1rXtBg-7Awx_F5MymJySZux_JIJSxKkaTFivK1xQZstqmNIKRr7PAcj8ZimeJ2m2KVZGo9f3vK57X929B-_p6ID</recordid><startdate>20220623</startdate><enddate>20220623</enddate><creator>Shrivastava, Gaurav</creator><creator>Valenzuela-Leon, Paola Carolina</creator><creator>Chagas, Andrezza Campos</creator><creator>Kern, Olivia</creator><creator>Botello, Karina</creator><creator>Zhang, Yixiang</creator><creator>Martin-Martin, Ines</creator><creator>Oliveira, Markus Berger</creator><creator>Tirloni, Lucas</creator><creator>Calvo, Eric</creator><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7670-2584</orcidid><orcidid>https://orcid.org/0000-0002-5740-5178</orcidid><orcidid>https://orcid.org/0000-0003-4582-7100</orcidid><orcidid>https://orcid.org/0000-0003-3229-4106</orcidid><orcidid>https://orcid.org/0000-0001-7880-2730</orcidid><orcidid>https://orcid.org/0000-0003-3577-5423</orcidid><orcidid>https://orcid.org/0000-0002-0956-7324</orcidid><orcidid>https://orcid.org/0000-0003-3422-8436</orcidid></search><sort><creationdate>20220623</creationdate><title>Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo</title><author>Shrivastava, Gaurav ; Valenzuela-Leon, Paola Carolina ; Chagas, Andrezza Campos ; Kern, Olivia ; Botello, Karina ; Zhang, Yixiang ; Martin-Martin, Ines ; Oliveira, Markus Berger ; Tirloni, Lucas ; Calvo, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c282t-f74467b079447227dd1bbef4c2af1d6798a0d830f8fb5bc6c27a1b9b9f5729a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aedes - metabolism</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anticoagulants - pharmacology</topic><topic>Cytokines</topic><topic>Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Interleukin-6</topic><topic>Mosquito Vectors</topic><topic>Receptor, PAR-1 - genetics</topic><topic>Receptor, PAR-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shrivastava, Gaurav</creatorcontrib><creatorcontrib>Valenzuela-Leon, Paola Carolina</creatorcontrib><creatorcontrib>Chagas, Andrezza Campos</creatorcontrib><creatorcontrib>Kern, Olivia</creatorcontrib><creatorcontrib>Botello, Karina</creatorcontrib><creatorcontrib>Zhang, Yixiang</creatorcontrib><creatorcontrib>Martin-Martin, Ines</creatorcontrib><creatorcontrib>Oliveira, Markus Berger</creatorcontrib><creatorcontrib>Tirloni, Lucas</creatorcontrib><creatorcontrib>Calvo, Eric</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>ImmunoHorizons</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shrivastava, Gaurav</au><au>Valenzuela-Leon, Paola Carolina</au><au>Chagas, Andrezza Campos</au><au>Kern, Olivia</au><au>Botello, Karina</au><au>Zhang, Yixiang</au><au>Martin-Martin, Ines</au><au>Oliveira, Markus Berger</au><au>Tirloni, Lucas</au><au>Calvo, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo</atitle><jtitle>ImmunoHorizons</jtitle><addtitle>Immunohorizons</addtitle><date>2022-06-23</date><risdate>2022</risdate><volume>6</volume><issue>6</issue><spage>373</spage><epage>383</epage><pages>373-383</pages><issn>2573-7732</issn><eissn>2573-7732</eissn><abstract>Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector
, is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding.</abstract><cop>United States</cop><pmid>35738824</pmid><doi>10.4049/immunohorizons.2200045</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7670-2584</orcidid><orcidid>https://orcid.org/0000-0002-5740-5178</orcidid><orcidid>https://orcid.org/0000-0003-4582-7100</orcidid><orcidid>https://orcid.org/0000-0003-3229-4106</orcidid><orcidid>https://orcid.org/0000-0001-7880-2730</orcidid><orcidid>https://orcid.org/0000-0003-3577-5423</orcidid><orcidid>https://orcid.org/0000-0002-0956-7324</orcidid><orcidid>https://orcid.org/0000-0003-3422-8436</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aedes - metabolism Animals Anti-Inflammatory Agents - pharmacology Anticoagulants - pharmacology Cytokines Endothelial Cells - metabolism Humans Interleukin-6 Mosquito Vectors Receptor, PAR-1 - genetics Receptor, PAR-1 - metabolism |
title | Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo |
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