Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recru...
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MDPI AG
2017-04-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/9/4/125 |
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| author | José M. Rojas Tomás Arán-Sekul Emmanuel Cortés Romina Jaldín Kely Ordenes Patricio R. Orrego Jorge González Jorge E. Araya Alejandro Catalán |
| author_facet | José M. Rojas Tomás Arán-Sekul Emmanuel Cortés Romina Jaldín Kely Ordenes Patricio R. Orrego Jorge González Jorge E. Araya Alejandro Catalán |
| author_sort | José M. Rojas |
| collection | DOAJ |
| description | Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active) and rLlPLD2 (inactive) isoforms induce interleukin (IL)-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1) expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism. |
| first_indexed | 2024-04-11T22:50:48Z |
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| id | doaj.art-733f1ff2c33a4c578c9e009a90faafa3 |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T22:50:48Z |
| publishDate | 2017-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-733f1ff2c33a4c578c9e009a90faafa32022-12-22T03:58:35ZengMDPI AGToxins2072-66512017-04-019412510.3390/toxins9040125toxins9040125Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes MigrationJosé M. Rojas0Tomás Arán-Sekul1Emmanuel Cortés2Romina Jaldín3Kely Ordenes4Patricio R. Orrego5Jorge González6Jorge E. Araya7Alejandro Catalán8Laboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileDepartamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileLaboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileCutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active) and rLlPLD2 (inactive) isoforms induce interleukin (IL)-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1) expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism.http://www.mdpi.com/2072-6651/9/4/125phospholipase DLoxosceles laetamonocytes migrationchemokines |
| spellingShingle | José M. Rojas Tomás Arán-Sekul Emmanuel Cortés Romina Jaldín Kely Ordenes Patricio R. Orrego Jorge González Jorge E. Araya Alejandro Catalán Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration Toxins phospholipase D Loxosceles laeta monocytes migration chemokines |
| title | Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration |
| title_full | Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration |
| title_fullStr | Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration |
| title_full_unstemmed | Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration |
| title_short | Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration |
| title_sort | phospholipase d from loxosceles laeta spider venom induces il 6 il 8 cxcl1 gro α and ccl2 mcp 1 production in human skin fibroblasts and stimulates monocytes migration |
| topic | phospholipase D Loxosceles laeta monocytes migration chemokines |
| url | http://www.mdpi.com/2072-6651/9/4/125 |
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