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Article

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

by
Sayonara Ivana Santos de Assis
1,
Leonardo Szalo Amendola
1,
Maristela Mitiko Okamoto
2,
Guilherme da Silva Ferreira
1,
Rodrigo Tallada Iborra
3,
Danielle Ribeiro Santos
1,
Monique de Fátima Mello Santana
1,
Kelly Gomes Santana
1,
Maria Lucia Correa-Giannella
4,
Denise Frediani Barbeiro
5,
Francisco Garcia Soriano
5,
Ubiratan Fabres Machado
2 and
Marisa Passarelli
1,6,*
1
Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil
2
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
3
Ciências Biológicas e da Saúde, Campos Mooca, Universidade São Judas Tadeu, São Paulo 03408-050, Brazil
4
Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil
5
Laboratório de Emergências Clínicas (LIM 51), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil
6
Programa de Pós-Graduação em Medicina, Universidade Nove de Julho, São Paulo 01525-000, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(5), 2713; https://doi.org/10.3390/ijms25052713
Submission received: 2 February 2024 / Revised: 20 February 2024 / Accepted: 23 February 2024 / Published: 27 February 2024
(This article belongs to the Special Issue New Advances in Inflammasomes)
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Abstract

Advanced 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.
Keywords: advanced glycation end products; NFKB; RAGE; toll-like receptor; lipopolysaccharide; inflammation advanced glycation end products; NFKB; RAGE; toll-like receptor; lipopolysaccharide; inflammation

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MDPI and ACS Style

Assis, S.I.S.d.; Amendola, L.S.; Okamoto, M.M.; Ferreira, G.d.S.; Iborra, R.T.; Santos, D.R.; Santana, M.d.F.M.; Santana, K.G.; Correa-Giannella, M.L.; Barbeiro, D.F.; et al. 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. Int. J. Mol. Sci. 2024, 25, 2713. https://doi.org/10.3390/ijms25052713

AMA Style

Assis SISd, Amendola LS, Okamoto MM, Ferreira GdS, Iborra RT, Santos DR, Santana MdFM, Santana KG, Correa-Giannella ML, Barbeiro DF, et al. 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. International Journal of Molecular Sciences. 2024; 25(5):2713. https://doi.org/10.3390/ijms25052713

Chicago/Turabian Style

Assis, Sayonara Ivana Santos de, Leonardo Szalo Amendola, Maristela Mitiko Okamoto, Guilherme da Silva Ferreira, Rodrigo Tallada Iborra, Danielle Ribeiro Santos, Monique de Fátima Mello Santana, Kelly Gomes Santana, Maria Lucia Correa-Giannella, Denise Frediani Barbeiro, and et al. 2024. "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" International Journal of Molecular Sciences 25, no. 5: 2713. https://doi.org/10.3390/ijms25052713

APA Style

Assis, S. I. S. d., Amendola, L. S., Okamoto, M. M., Ferreira, G. d. S., Iborra, R. T., Santos, D. R., Santana, M. d. F. M., Santana, K. G., Correa-Giannella, M. L., Barbeiro, D. F., Soriano, F. G., Machado, U. F., & Passarelli, M. (2024). 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. International Journal of Molecular Sciences, 25(5), 2713. https://doi.org/10.3390/ijms25052713

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