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Open AccessArticle

Inflammasome Activation Induced by a Snake Venom Lys49-Phospholipase A2 Homologue

1
Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, 76812-245 Porto Velho-RO, Brazil
2
Centro de Estudos de Biomoléculas Aplicadas à Saúde (CEBio), Fundação Oswaldo Cruz, FIOCRUZ Rondônia e Departamento de Medicina, Universidade Federal de Rondônia, UNIR, 76812-245 Porto Velho-RO, Brazil
3
Centro Universitário São Lucas, UniSL, 76805-846 Porto Velho, RO, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(1), 22; https://doi.org/10.3390/toxins12010022
Received: 25 November 2019 / Revised: 12 December 2019 / Accepted: 26 December 2019 / Published: 31 December 2019
(This article belongs to the Section Animal Venoms)
Background: Snake venom phospholipases A2 (PLA2s) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA2 isolated from Bothrops jararacussu venom, is an example of Lys49-PLA2 that presents such actions. NLRP3 is a cytosolic receptor from the NLR family responsible for inflammasome activation via caspase-1 activation and IL-1β liberation. The study of NLRs that recognize tissue damage and activate the inflammasome is relevant in envenomation. Methods: Male mice (18–20 g) received an intramuscular injection of BthTX-I or sterile saline. The serum was collected for creatine-kinase (CK), lactate dehydrogenase (LDH), and interleukin-1β (IL-1β) assays, and muscle was removed for inflammasome activation immunoblotting and qRT-PCR expression for nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin-containing domain 3 receptor (NLRP3) inflammasome components. Results: BthTX-I-induced inflammation and myonecrosis, shown by intravital microscope, and LDH and CK release, respectively. Mouse treatment with A438079, a P2X7 receptor antagonist, did not modify these effects. BthTX-I induced inflammasome activation in muscle, but P2X7R participation in this effect was not observed. Conclusion: Together, the results showed for the first time that BthTX-I in gastrocnemius muscle induces inflammation and consequently, inflammasome activation via NLRP3 with caspase-1 activation and IL-1β liberation. View Full-Text
Keywords: snake venom; Lys49-PLA2; muscle; inflammasome snake venom; Lys49-PLA2; muscle; inflammasome
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Boeno, C.N.; Paloschi, M.V.; Lopes, J.A.; Pires, W.L.; Setúbal, S.S.; Evangelista, J.R.; Soares, A.M.; Zuliani, J.P. Inflammasome Activation Induced by a Snake Venom Lys49-Phospholipase A2 Homologue. Toxins 2020, 12, 22.

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