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

Autor(es)

Tripodi, Gustavo Luis ^[1] ; Prieto, Marcela Bach ^[1] ; Abdalla, Dulcineia Saes Parra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inflammation; v. 43, n. 2, p. 722-730, APR 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 12/51316-5 - Investigação da atividade de biofármacos, agonistas de PPARs e produtos naturais com potencial terapêutico na aterosclerose
• Beneficiário: Dulcineia Saes Parra Abdalla
• Modalidade de apoio: Auxílio à Pesquisa - Temático