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Toxins 2017, 9(4), 125; doi:10.3390/toxins9040125

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

1
Laboratorio de Parasitología Molecular, Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, Chile
2
Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, CP 1270300, Chile
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Andreimar M. Soares
Received: 18 December 2016 / Revised: 16 March 2017 / Accepted: 28 March 2017 / Published: 5 April 2017
(This article belongs to the Section Animal Venoms)
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Abstract

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. View Full-Text
Keywords: phospholipase D; Loxosceles laeta; monocytes migration; chemokines phospholipase D; Loxosceles laeta; monocytes migration; chemokines
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Rojas, J.M.; Arán-Sekul, T.; Cortés, E.; Jaldín, R.; Ordenes, K.; Orrego, P.R.; González, J.; Araya, J.E.; Catalán, A. 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 2017, 9, 125.

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