Sphingomyelinase D from Loxosceles laeta Venom Induces the Expression of MMP7 in Human Keratinocytes: Contribution to Dermonecrosis

Mara A Corrêa; Cinthya K Okamoto; Rute M Gonçalves-de-Andrade; Carmen W van den Berg; Denise V Tambourgi

doi:10.1371/journal.pone.0153090

Sphingomyelinase D from Loxosceles laeta Venom Induces the Expression of MMP7 in Human Keratinocytes: Contribution to Dermonecrosis

PLoS One. 2016 Apr 14;11(4):e0153090. doi: 10.1371/journal.pone.0153090. eCollection 2016.

Authors

Mara A Corrêa¹, Cinthya K Okamoto¹, Rute M Gonçalves-de-Andrade¹, Carmen W van den Berg², Denise V Tambourgi¹

Affiliations

¹ Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
² Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom.

Abstract

Envenomation by Loxosceles spider is characterized by the development of dermonecrosis. In previous studies, we have demonstrated that increased expression/secretion of matrix metalloproteinases 2 and 9, induced by Loxosceles intermedia venom Class 2 SMases D (the main toxin in the spider venom), contribute to the development of cutaneous loxoscelism. In the present study we show that the more potent venom containing the Class 1 SMase D from Loxosceles laeta, in addition to increasing the expression/secretion of MMP2 and MMP9, also stimulates the expression of MMP7 (Matrilysin-1), which was associated with keratinocyte cell death. Tetracycline, a matrix metalloproteinase inhibitor, prevented cell death and reduced MMPs expression. Considering that L. laeta venom is more potent at inducing dermonecrosis than L. intermedia venom, our results suggest that MMP7 may play an important role in the severity of dermonecrosis induced by L. laeta spider venom SMase D. In addition, the inhibition of MMPs by e.g. tetracyclines may be considered for the treatment of the cutaneous loxoscelism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Apoptosis / drug effects
Arthropod Proteins / pharmacology*
Blotting, Western
Cell Line
Cell Survival / drug effects
Dose-Response Relationship, Drug
Humans
Keratinocytes / drug effects*
Keratinocytes / metabolism
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 7 / metabolism
Matrix Metalloproteinase 9 / metabolism
Necrosis / prevention & control
Phosphoric Diester Hydrolases / pharmacology*
Rabbits
Skin / drug effects
Skin / pathology
Spider Venoms / enzymology
Spider Venoms / pharmacology*
Spiders / enzymology*
Tetracycline / pharmacology
Time Factors

Substances

Anti-Bacterial Agents
Arthropod Proteins
Spider Venoms
Phosphoric Diester Hydrolases
sphingomyelin phosphodiesterase D
Matrix Metalloproteinase 7
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Tetracycline

Grants and funding

This work was supported by funds from Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (FAPESP), CeTICS Program FAPESP (2013/07467-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.