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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inflammasome Activation in Human Macrophages Induced by a LDL (-) Mimetic Peptide

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Author(s):
Tripodi, Gustavo Luis [1] ; Prieto, Marcela Bach [1] ; Abdalla, Dulcineia Saes Parra [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Inflammation; v. 43, n. 2, p. 722-730, APR 2020.
Web of Science Citations: 0
Abstract

Abstract The inflammasome is responsible for maturation of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18) contributing to the inflammatory process in atherosclerosis. It is shown here that an electronegative low-density lipoprotein {[}LDL (-)] apoB-100 mimetic peptide can activate the transcriptional and posttranslational signs needed for complete inflammasome activation. This peptide, named p2C7, can activate the Toll-like receptor 4 (TLR4) that induces NF-kappa B activation and the transcription of inflammasome components. After blocking TLR4 with a neutralizing antibody, inflammasome component (NLRP3, CASP1, and ASC) and IL1b and IL18 gene downregulation occurred in human-derived macrophages stimulated with p2C7 or LDL (-). Moreover, the posttranslational signal was activated by the interaction between p2C7 and the lectin-type oxidized LDL receptor 1 (LOX-1), as demonstrated by the induction of caspase-1 cleavage in macrophages. The blockage of either TLR4 or LOX-1 decreased IL-1 beta and IL-18 secretion by human-derived macrophages as both pathways are necessary for complete inflammasome activation. These findings suggest a mechanism by which macrophages transduce the pro-inflammatory signal provided by LDL (-) ApoB-100 and its mimetic peptides to activate the inflammasome protein complex what may be relevant for the inflammatory process in atherosclerosis. (AU)

FAPESP's process: 12/51316-5 - Study of the activity of biodrugs, PPARs agonists and natural products with therapeutic potential in atherosclerosis
Grantee:Dulcineia Saes Parra Abdalla
Support Opportunities: Research Projects - Thematic Grants