Suppression of Lipopolysaccharide-Induced IL-1ß Gene Expression by High-Molecular-Weight Adiponectin in RAW264.7 Macrophages.
Biol Pharm Bull
; 46(11): 1498-1505, 2023.
Article
in En
| MEDLINE
| ID: mdl-37914352
ABSTRACT
Adiponectin is an abundant adipocytokine secreted by adipocytes. It exists in the plasma in its trimeric, hexameric, high-molecular-weight (HMW), and globular (a proteolytic product) isoforms. Adiponectin's anti-inflammatory effects on macrophages remain controversial. We have previously reported a simple and effective method for purifying native HMW adiponectin from human plasma. Here, we investigated whether native HMW adiponectin from human plasma has anti-inflammatory effects on macrophages. Pretreatment with human native HMW adiponectin inhibited lipopolysaccharide (LPS)-induced interleukin-1ß (IL-1ß) gene expression, but not tumor necrosis factor (TNF)-α expression. However, simultaneous treatment with HMW adiponectin and LPS did not inhibit IL-1ß expression. Further, HMW adiponectin pretreatment decreases glycogen synthase kinase-3ß (GSK-3ß) inactivation by abrogating LPS-induced Akt (Ser473) phosphorylation, which subsequently suppresses LPS-induced CCAAT/enhancer binding protein ß (C/EBPß) protein translation and nuclear translocation. However, HMW adiponectin pretreatment did not affect LPS-induced nuclear factor-kappaB (NF-κB) activation. These results suggest that HMW adiponectin mediates potent anti-inflammatory activities in macrophages by inhibiting its Akt-C/EBPß signaling pathway, thereby suppressing IL-1ß gene expression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Adiponectin
Limits:
Humans
Language:
En
Journal:
Biol Pharm Bull
Journal subject:
BIOQUIMICA
/
FARMACOLOGIA
Year:
2023
Document type:
Article