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
| Autor: | Alejandro Catalán, Jorge E. Araya, Kely Ordenes, Emmanuel Cortés, Tomás Arán-Sekul, Jorge González, José M. Rojas, Patricio R. Orrego, Romina Jaldín |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Leukocyte migration monocytes migration Health Toxicology and Mutagenesis Loxosceles laeta lcsh:Medicine Spider Venoms chemokines CCL2 Ceramides Toxicology Monocytes Article Arthropod Proteins Cell Line 03 medical and health sciences chemistry.chemical_compound Cell Movement Lysophosphatidic acid Phospholipase D medicine Animals Humans RNA Messenger phospholipase D Skin biology Monocyte lcsh:R Interleukin Spiders Chemotaxis Fibroblasts Molecular biology Recombinant Proteins 030104 developmental biology medicine.anatomical_structure chemistry Immunology biology.protein Cytokines Lysophospholipids |
| Zdroj: | Toxins; Volume 9; Issue 4; Pages: 125 Toxins Toxins, Vol 9, Iss 4, p 125 (2017) |
| ISSN: | 2072-6651 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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