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

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153090
• Main Authors: Corrêa, Mara A, Okamoto, Cinthya K, Gonçalves-de-Andrade, Rute M, van den Berg, Carmen W, Tambourgi, Denise V
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Apoptosis - drug effects; Arthropod Proteins - pharmacology; Biology and Life Sciences; Blotting, Western; Cell death; Cell Line; Cell Survival - drug effects; Dermatology; Dose-Response Relationship, Drug; Enzymes; Gelatinase A; Gelatinase B; Gene expression; Genetic aspects; Humans; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Laboratories; Matrilysin; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 7 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Medicine and Health Sciences; Metalloenzymes; Metalloproteinase; Necrosis - prevention & control; Phosphoric Diester Hydrolases - pharmacology; Physiological aspects; Rabbits; Research and Analysis Methods; Secretion; Skin - drug effects; Skin - pathology; Sphingomyelin phosphodiesterase; Spider Venoms - enzymology; Spider Venoms - pharmacology; Spiders; Spiders - enzymology; Tetracycline - pharmacology; Tetracyclines; Time Factors; Venom; Venoms
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153090

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.