Plasma Oxylipins Levels in Nonalcoholic Fatty Liver Disease.
Dig Dis Sci
; 65(12): 3605-3613, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-31997053
ABSTRACT
BACKGROUND:
Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD-associated lipid disturbances and polyunsaturated fatty acid (PUFA) metabolism in particular contribute to heightened innate immunity, remains to be determined.OBJECTIVE:
To determine if oxylipins, metabolic products of PUFA metabolism, enhance innate immune reactivity alone and/or following exposure to LPS.METHODS:
Plasma and peripheral blood mononuclear cells (PBMC) were collected from 35 NAFLD patients and 8 healthy controls. Oxylipin levels were documented by HPLC-MS/MS, cytokines (IL-1, IL-6, IL-10, and TNF-α) by ELISA, and chemokine receptors (CCR1 and CCR2) by flow cytometry.RESULTS:
Mean plasma levels of four pro-inflammatory oxylipins (Tetranor 12-HETE, 20-HETE, 8-HETrE, and 7-HDoHE) were significantly elevated in NAFLD patients compared to healthy controls. However, the levels did not correlate with the severity of liver injury as reflected by serum aminotransferases, ck18M30, and Fib-4 determinations. In vitro, 20-HETE (0.01-100 nM), the plasma oxylipin with the most significantly elevated plasma levels, did not alter NAFLD or control PBMC cytokine release or enhance the increases in cytokine release following 24 h of LPS exposure. Similarly, 20-HETE alone did not alter PBMC CCR1 or CCR2 expression or LPS-induced downregulation of these receptors.CONCLUSIONS:
Pro-inflammatory oxylipin levels are increased in NAFLD, but these metabolites do not appear to drive short-term direct or LPS-induced increases in PBMC cytokine release or chemotaxis.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Citocinas
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Receptores de Quimiocinas
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Oxilipinas
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Hepatopatia Gordurosa não Alcoólica
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá