title: Sphingomyelinase D from Loxosceles laeta Venom Induces the Expression of MMP7 in Human Keratinocytes: Contribution to Dermonecrosis.
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.
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
authors.forename: Mara A
authors.initials: MA
authors.lastname: Corrêa
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
authors.forename: Cinthya K
authors.initials: CK
authors.lastname: Okamoto
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
authors.forename: Rute M
authors.initials: RM
authors.lastname: Gonçalves-de-Andrade
authors.affiliation: Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Carmen W
authors.initials: CW
authors.lastname: van den Berg
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
authors.forename: Denise V
authors.initials: DV
authors.lastname: Tambourgi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D060829:Arthropod Proteins / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009336:Necrosis / Q000517:prevention & control; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology*; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013111:Spider Venoms / Q000201:enzymology / Q000494:pharmacology*; D013112:Spiders / Q000201:enzymology*; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D060829:Arthropod Proteins; D013111:Spider Venoms; D010727:Phosphoric Diester Hydrolases; C055160:sphingomyelin phosphodiesterase D; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013752:Tetracycline