Study of inflamassomes activation, in human keratinocytes, by Loxosceles laeta spider venom and its sphingomyelinase D

• Grant number: 15/17053-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2016
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Denise Vilarinho Tambourgi
• Grantee: Priscila Hess Lopes
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

The inflammasomes are multiprotein complexes able to sense danger signals derived from pathogens or endogenous signs of cell stress. The activation of these complexes promotes rapid conversion of the caspase-1 zymogen in the active enzyme, which in turn acts on cytokines maturation, as IL-1² and IL-18, and induces a type of programmed cell death with inflammatory characteristics, named as pyroptosis. Various components in venoms exhibit cytotoxic activities that depend on their ability to bind and disrupt cell membranes; so, it is possible that venoms can induce inflammasome activation; however, r, there are few studies investigating the innate recognition of animal venoms. Some inflammatory loxoscelism characteristics, such as IL-1² production and superoxide generation, suggesting that recognition of this poison / toxin by the innate immune system in keratinocytes by inflammasomes activation occurs, initiating an inflammatory cascade of events that culminates in the development the necrotic lesion. This study aims to investigate the possible activation inflammasomes by Loxosceles laeta venom and its central toxin, the SMase D. in human keratinocytes, and to verify the influence of activation in cell death induced by the venom / toxin, and investigate the influence of ROS generation by the venom/toxin in the inflammasomes activation.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOPES, PRISCILA HESS; ROCHA, MARISA M. T.; KUNIYOSHI, ALEXANDRE KAZUO; VIEIRA PORTARO, FERNANDA CALHETA; GONCALVES, LUIS ROBERTO C.. Edema and Nociception Induced by Philodryas patagoniensis Venom in Mice: A Pharmacological Evaluation with Implications for the Accident Treatment. Journal of Pharmacology and Experimental Therapeutics, v. 361, n. 3, p. 349-354, JUN 1 2017. (15/17053-5, 13/15344-7)

DA SILVA, MARCELO SANTOS; LOPES, PRISCILA HESS; ELIAS, MARIA CAROLINA; TAMBOURGI, V, DENISE. Cytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venom. ARCHIVES OF TOXICOLOGY, v. 94, n. 10, JUN 2020. (15/17053-5, 13/07467-1, 14/24170-5)

LOPES, PRISCILA HESS; FUKUSHIMA, CAROLINE SAYURI; SHOJI, ROSANA; BERTANI, ROGERIO; TAMBOURGI, V, DENISE. Searching for the toxic potential of Loxosceles amazonica and Loxosceles willianilsoni spiders' venoms. Toxicon, v. 191, p. 1-8, FEB 2021. (15/17053-5, 13/07467-1)

LOPES, PRISCILA HESS; FUKUSHIMA, CAROLINE SAYURI; SHOJI, ROSANA; BERTANI, ROGERIO; TAMBOURGI, V, DENISE. Sphingomyelinase D Activity in Sicarius tropicus Venom: Toxic Potential and Clues to the Evolution of SMases D in the Sicariidae Family. TOXINS, v. 13, n. 4, APR 2021. (15/17053-5, 13/07467-1)

LOPES, PRISCILA HESS; SQUAIELLA-BAPTISTAO, CARLA CRISTINA; MARQUES, MARIO OCTAVIO THA; TAMBOURGI, DENISE V.. Clinical aspects, diagnosis and management of Loxosceles spider envenomation: literature and case review. ARCHIVES OF TOXICOLOGY, v. 94, n. 5, MAR 2020. (13/07467-1, 15/17053-5)

LOPES, PRISCILA HESS; VAN DEN BERG, CARMEN W.; TAMBOURGI, V, DENISE. Sphingomyelinases D From Loxosceles Spider Venoms and Cell Membranes: Action on Lipid Rafts and Activation of Endogenous Metalloproteinases. FRONTIERS IN PHARMACOLOGY, v. 11, MAY 13 2020. (13/07467-1, 15/17053-5)

LOPES, PRISCILA HESS; MURAKAMI, MARIO T.; PORTARO, V, FERNANDA C.; MESQUITA PASQUALOTO, KERLY FERNANDA; VAN DEN BERG, CARMEN; TAMBOURGI, V, DENISE. Targeting Loxosceles spider Sphingomyelinase D with small-molecule inhibitors as a potential therapeutic approach for loxoscelism. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 34, n. 1, p. 310-321, JAN 1 2019. (13/07467-1, 08/57898-0, 15/17053-5)

MANZONI-DE-ALMEIDA, DANIEL; SQUAIELLA-BAPTISTAO, CARLA CRISTINA; LOPES, PRISCILA HESS; VAN DEN BERG, CARMEN W.; TAMBOURGI, DENISE V.. Loxosceles venom Sphingomyelinase D activates human blood leukocytes: Role of the complement system. Molecular Immunology, v. 94, p. 45-53, FEB 2018. (13/07467-1, 15/17053-5)