title: Role of matrix metalloproteinases in HaCaT keratinocytes apoptosis induced by loxosceles venom sphingomyelinase D.
abstract: Envenomation by the spider Loxosceles (brown spider) can result in dermonecrosis and severe ulceration. We have previously shown that Loxosceles sphingomyelinase D (SMaseD), the enzyme responsible for these pathological effects, induced expression of matrix metalloproteinase-9 (MMP-9), which is possibly one of the main factors involved in the pathogenesis of the cutaneous loxoscelism. The aim of this study was to further investigate the molecular mechanisms triggered by Loxosceles SMaseD involved in the initiation of the dermonecrotic lesion, using HaCaT cultures, a human keratinocyte cell line, as an in vitro model for cutaneous loxoscelism. We show here that SMaseD from Loxosceles spider venom induces apoptosis in human keratinocytes, which is associated with an increased expression of metalloproteinase-2 and -9, and that the use of metalloproteinase inhibitors, such as tetracycline, may prevent cell death and potentially may prevent tissue destruction after envenomation.
authors.affiliation: Laboratório de Imunoquímica, Instituto Butantan, São Paulo, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Paixão-Cavalcante
authors.forename: Carmen W
authors.initials: CW
authors.lastname: van den Berg
authors.forename: Matheus
authors.initials: M
authors.lastname: de Freitas Fernandes-Pedrosa
authors.forename: Rute M
authors.initials: RM
authors.lastname: Gonçalves de Andrade
authors.forename: Denise V
authors.initials: DV
authors.lastname: Tambourgi
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002461:Cell Line, Transformed; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology*; D011419:Propidium / Q000378:metabolism; D013111:Spider Venoms / Q000201:enzymology*
chemical_list: D017304:Annexin A5; D015415:Biomarkers; D013111:Spider Venoms; C055161:loxosceles venom; D011419:Propidium; D010727:Phosphoric Diester Hydrolases; C055160:sphingomyelin phosphodiesterase D; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9