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Effect of NLRP3 deficiency on cytotoxic and IL-1β-producing activities of synthetic candidalysin peptide.
- Source :
- Journal of Oral Biosciences; Dec2023, Vol. 65 Issue 4, p287-292, 6p
- Publication Year :
- 2023
-
Abstract
- Candidalysin (CL), a hydrophobic peptide toxin secreted by Candida albicans , is a key virulence factor that contributes to cytolysis, tissue damage, and immune activation. CL is thought to exert some of its biological activities, including IL-1β production, through the activation of the NLRP3-inflammasome pathway. To date, the mechanism by which CL affects human NLRP3 is not fully understood. We investigated specific activities of synthetic CL peptides using human-derived NLRP3-deficient cells. Two distinct synthetic CL peptide solutions were prepared: CLd, with CL completely solubilized as nanoparticles in dimethyl sulfoxide, and CLw, with CL partly solubilized in water, and including insoluble microparticles. THP-1 human monocytic cells and NLRP3-deficient THP-1 cells were differentiated into macrophages and stimulated with these peptide solutions. Cell membrane damage, lactate dehydrogenase release, IL-1β production, and caspase-1 activation in stimulated cells were subsequently evaluated. Both CLd and CLw exhibited cytotoxic activities independent of NLRP3. Importantly, CLd induced IL-1β production and caspase-1 activation in an NLRP3-independent manner, whereas these activities in CLw-stimulated cells were entirely NLRP3-dependent, suggesting that the NLRP3-dependent response might be triggered by insoluble microparticles. Our results demonstrate that inherent CL activities can cause cell damage and IL-1β production in an NLRP3-independent manner. Our research advances the elucidation of the role of NLRP3 in CL biological activity, underscoring the necessity for further exploration of the precise mechanisms underlying the NLRP3-independent effects of CL and providing novel insights into the complexity of host–pathogen interactions. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13490079
- Volume :
- 65
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Journal of Oral Biosciences
- Publication Type :
- Academic Journal
- Accession number :
- 173473736
- Full Text :
- https://doi.org/10.1016/j.job.2023.08.007