Mariana Migliorini Parisi1,2, Lucas Kich Grun1,2, Patrícia Lavandoski1, Letícia Biscaino Alves3, Ivi Juliana Bristot2,4, Rita Mattiello5, Cláudio Corá Mottin3, Fábio Klamt2,4, Marcus Herbert Jones5, Alexandre Vontobel Padoin3, Fátima Costa Rodrigues Guma6, Florencia María Barbé-Tuana1,2. 1. Laboratory of Molecular Biology and Bioinformatics, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 2. Postgraduate Program of Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 3. Center of Obesity and Metabolic Syndrome, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. 4. Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 5. Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. 6. Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, ICBS/Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Abstract
OBJECTIVE: To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC). METHODS: Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture. RESULTS: Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction. After 120 hours, there was a higher secretion of inflammatory cytokines IL-1β and IL-8. CD8+ T lymphocytes presented decreased expression of CD28, which is associated with the immunosenescent phenotype. CD14+ macrophages showed increased expression of CD80 and CD206, suggesting a modulation in the activation of macrophages. CONCLUSIONS: These results demonstrate that chronic systemic inflammation observed in obesity induces dysfunctional features in PBMC that are consistent with premature immunosenescence.
OBJECTIVE: To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC). METHODS: Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture. RESULTS: Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction. After 120 hours, there was a higher secretion of inflammatory cytokines IL-1β and IL-8. CD8+ T lymphocytes presented decreased expression of CD28, which is associated with the immunosenescent phenotype. CD14+ macrophages showed increased expression of CD80 and CD206, suggesting a modulation in the activation of macrophages. CONCLUSIONS: These results demonstrate that chronic systemic inflammation observed in obesity induces dysfunctional features in PBMC that are consistent with premature immunosenescence.
Authors: Alyssa L Thomas; Pablo C Alarcon; Senad Divanovic; Claire A Chougnet; David A Hildeman; Maria E Moreno-Fernandez Journal: Front Aging Date: 2021-09-22