Texto completo
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Autor(es): |
Komegae, Evilin N.
[1]
;
Fonseca, Monique T.
[1]
;
Cruz-Machado, Sanseray da Silveira
[2]
;
Turato, Walter M.
[3]
;
Filgueiras, Luciano R.
[1]
;
Markus, Regina P.
[2]
;
Steiner, Alexandre A.
[1]
Número total de Autores: 7
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Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmunol Sepsis Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biosci, Lab Chronopharmacol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil
Número total de Afiliações: 3
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Tipo de documento: |
Artigo Científico
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Fonte: |
FRONTIERS IN IMMUNOLOGY;
v. 10,
JUN 28 2019.
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Citações Web of Science: |
0
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Resumo |
The mechanisms by which obesity may alter immune responses to pathogens are poorly understood. The present study assessed whether the intrinsic responsiveness of resident macrophages to bacterial lipopolysaccharide (LPS) is reprogrammed in high-fat diet (HFD)-induced obesity. Macrophages from adipose tissue, lung alveoli, and the peritoneal cavity were extracted fromobese rats on a HFD or fromtheir lean counterparts, and subsequently studied in culture under identical conditions. CD45(+)/CD68(+) cells (macrophages) were abundant in all cultures, and became the main producers of TNF-alpha upon LPS stimulation. But although all macrophage subpopulations responded to LPS with an M1-like profile of cytokine secretion, the TNF-alpha/IL-10 ratio was the lowest in adipose tissue macrophages, the highest in alveolar macrophages, and intermediary in peritoneal macrophages. What is more, diet exerted qualitatively distinct effects on the cytokine responses to LPS, with obesity switching adipose tissue macrophages to a more pro-inflammatory program and peritoneal macrophages to a less pro-inflammatory program, while not affecting alveolar macrophages. Such reprogramming was not associated with changes in the inflammasome-dependent secretion of IL-1 beta. The study further shows that the effects of diet on TNF-alpha/IL-10 ratios were linked to distinct patterns of NF-kappa B accumulation in the nucleus: while RelA was the NF-kappa B subunit most impacted by obesity in adipose tissue macrophages, cRel was the subunit affected in peritoneal macrophages. It is concluded that obesity causes dissimilar, site-specific changes in the responsiveness of resident macrophages to bacterial LPS. Such plasticity opens new avenues of investigation into the mechanisms linking obesity to pathogen-induced immune responses. (AU) |
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Processo FAPESP: |
12/03831-8 - Elo entre balanço energético e inflamação sistêmica: papel da leptina
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Beneficiário: | Alexandre Alarcon Steiner |
Linha de fomento: |
Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
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Processo FAPESP: |
18/03418-0 - Hipotermia na Sepse: causas e consequências
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Beneficiário: | Alexandre Alarcon Steiner |
Linha de fomento: |
Auxílio à Pesquisa - Temático
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Processo FAPESP: |
14/03719-9 - Papel da leptina na regulação da inflamação sistêmica
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Beneficiário: | Evilin Naname Komegae |
Linha de fomento: |
Bolsas no Brasil - Pós-Doutorado
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Processo FAPESP: |
13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
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Beneficiário: | Regina Pekelmann Markus |
Linha de fomento: |
Auxílio à Pesquisa - Temático
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Processo FAPESP: |
15/04557-5 - A ativação do eixo imune-pineal por dieta rica em lipídeos
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Beneficiário: | Sanseray da Silveira Cruz Machado |
Linha de fomento: |
Bolsas no Brasil - Pós-Doutorado
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Processo FAPESP: |
16/04921-1 - Tônus arterial no choque séptico: uma nova vertente para um velho problema.
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Beneficiário: | Alexandre Alarcon Steiner |
Linha de fomento: |
Auxílio à Pesquisa - Regular
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Processo FAPESP: |
17/13350-0 - A temperatura regula negativamente a atividade microbicida de macrófagos: por que eles matam mais na hipotermia?
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Beneficiário: | Monique Thaís Costa Fonseca |
Linha de fomento: |
Bolsas no Brasil - Pós-Doutorado
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Processo FAPESP: |
14/17407-9 - Programas moleculares envolvidos no equilíbrio da expressão de SOCS-1/MyD88 em macrófagos de diabéticos e consequência na resposta à infecção
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Beneficiário: | Luciano Filgueiras Ribeiro Junior |
Linha de fomento: |
Bolsas no Brasil - Pós-Doutorado
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