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

Overview
Journal Toxins (Basel)
Publisher MDPI
Specialty Toxicology
Date 2020 Jan 8
PMID 31906173
Citations 5
Authors
Affiliations
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Abstract

Background: Snake venom phospholipases A (PLAs) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA isolated from venom, is an example of Lys49-PLA 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.

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References
1.
Idzko M, Ferrari D, Eltzschig H . Nucleotide signalling during inflammation. Nature. 2014; 509(7500):310-7. PMC: 4222675. DOI: 10.1038/nature13085. View

2.
Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

3.
Pugin J . How tissue injury alarms the immune system and causes a systemic inflammatory response syndrome. Ann Intensive Care. 2012; 2(1):27. PMC: 3488542. DOI: 10.1186/2110-5820-2-27. View

4.
Piccini A, Carta S, Tassi S, Lasiglie D, Fossati G, Rubartelli A . ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc Natl Acad Sci U S A. 2008; 105(23):8067-72. PMC: 2430360. DOI: 10.1073/pnas.0709684105. View

5.
Lomonte B, Gutierrez J, Romero M, Nunez J, Tarkowski A, Hanson L . An MTT-based method for the in vivo quantification of myotoxic activity of snake venoms and its neutralization by antibodies. J Immunol Methods. 1993; 161(2):231-7. DOI: 10.1016/0022-1759(93)90299-m. View