The Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in Macrophages

Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPASSIS, Sayonara Ivana Santos deAMENDOLA, Leonardo SzaloOKAMOTO, Maristela MitikoFERREIRA, Guilherme da SilvaIBORRA, Rodrigo TalladaSANTOS, Danielle RibeiroSANTANA, Monique de Fatima MelloSANTANA, Kelly GomesCORREA-GIANNELLA, Maria LuciaBARBEIRO, Denise FredianiSORIANO, Francisco GarciaMACHADO, Ubiratan FabresPASSARELLI, Marisa2024-04-052024-04-052024INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.25, n.5, article ID 2713, 16p, 20241661-6596https://observatorio.fm.usp.br/handle/OPI/58797Advanced glycation end products (AGEs) prime macrophages for lipopolysaccharide (LPS)-induced inflammation. We investigated the persistence of cellular AGE-sensitization to LPS, considering the nuclear content of p50 and p65 nuclear factor kappa B (NFKB) subunits and the expression of inflammatory genes. Macrophages treated with control (C) or AGE-albumin were rested for varying intervals in medium alone before being incubated with LPS. Comparisons were made using one-way ANOVA or Student t-test (n = 6). AGE-albumin primed macrophages for increased responsiveness to LPS, resulting in elevated levels of TNF, IL-6, and IL-1beta (1.5%, 9.4%, and 5.6%, respectively), compared to C-albumin. TNF, IL-6, and IL-1 beta secretion persisted for up to 24 h even after the removal of AGE-albumin (area under the curve greater by 1.6, 16, and 5.2 times, respectively). The expressions of Il6 and RelA were higher 8 h after albumin removal, and Il6 and Abca1 were higher 24 h after albumin removal. The nuclear content of p50 remained similar, but p65 showed a sustained increase (2.9 times) for up to 24 h in AGE-albumin-treated cells. The prolonged activation of the p65 subunit of NFKB contributes to the persistent effect of AGEs on macrophage inflammatory priming, which could be targeted for therapies to prevent complications based on the AGE-RAGE-NFKB axis.engopenAccessadvanced glycation end productsNFKBRAGEtoll-like receptorlipopolysaccharideinflammationmetabolic-controloxidative stressgene-expressionreinstitutiondegradationproteinsreceptorThe Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in MacrophagesarticleCopyright MDPI10.3390/ijms25052713Biochemistry & Molecular BiologyChemistry, Multidisciplinary1422-0067