Metformin Down-regulates TNF-alpha Secretion via Suppression of Scavenger Receptors in Macrophages
Immune Network
;
: 123-132, 2013.
Article
in English
| WPRIM
| ID: wpr-77569
ABSTRACT
Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-alpha and the expressions of scavenger receptors.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Insulin Resistance
/
RNA, Messenger
/
Dinoprostone
/
Down-Regulation
/
Prevalence
/
Cytokines
/
NF-kappa B
/
Interleukin-4
/
Interleukin-6
/
Tumor Necrosis Factor-alpha
Type of study:
Prevalence study
Limits:
Animals
Language:
English
Journal:
Immune Network
Year:
2013
Type:
Article
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