Inhibition of p38mapk Reduces Adipose Tissue Inflammation in Aging Mediated by Arginase-II.
Pharmacology
; 105(9-10): 491-504, 2020.
Article
en En
| MEDLINE
| ID: mdl-32454488
ABSTRACT
BACKGROUND:
Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue inflammation and improves glucose tolerance in obesity. However, the role of Arg-II in aging adipose tissue inflammation is not clear.OBJECTIVE:
This study investigated the role of Arg-II in age-associated adipose tissue inflammation.METHODS:
Visceral adipose tissues of young (3-6 months) and old (20-24 months) wild-type (WT) and Arg-II-/- mice were investigated. Immunofluorescence confocal microscopy was performed for analysis of macrophage accumulation and cellular localization of arginase and cytokines; expression of arginase and cytokines was analyzed by qRT-PCR or immunoblotting or ELISA; activation of mitogen-activated protein kinases in adipose tissues was analyzed by immunoblotting; and arginase activity was measured by colorimetric determination of urea production.RESULTS:
In the old WT mice, there is more macrophage accumulation in the visceral adipose tissues than in Arg-II knockout animals. An age-associated increase in arginase activity and Arg-II expression in adipose tissues of WT mice is observed. Arg-II knockout enhances Arg-I expression and activity, but inhibits interleukin (IL)-6 expression and secretion and reduces active p38mapk in aging adipose tissue macrophages and stromal cells. Treatment of aging adipose tissues of WT mice with a specific p38mapk inhibitor SB203580 reduces IL-6 secretion.CONCLUSIONS:
Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Arginasa
/
Envejecimiento
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Tejido Adiposo
/
Proteínas Quinasas p38 Activadas por Mitógenos
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Pharmacology
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza