Metformin Down-regulates TNF-alpha Secretion via Suppression of Scavenger Receptors in Macrophages.
- Author:
Bobae HYUN
1
;
Seulmee SHIN
;
Aeri LEE
;
Sungwon LEE
;
Youngcheon SONG
;
Nam Joo HA
;
Kyung Hea CHO
;
Kyungjae KIM
Author Information
- Publication Type:Original Article
- Keywords: Metformin; Obesity-induced inflammation; TNF-alpha; Scavenger receptors
- MeSH: Animals; Cytokines; Diet, High-Fat; Dinoprostone; Down-Regulation; Hand; Inflammation; Insulin Resistance; Interleukin-10; Interleukin-4; Interleukin-6; Macrophages; Macrophages, Peritoneal; Metformin; Mice; Mice, Obese; NF-kappa B; Obesity; Prevalence; Receptors, Scavenger; RNA, Messenger; Tumor Necrosis Factor-alpha
- From:Immune Network 2013;13(4):123-132
- CountryRepublic of Korea
- Language:English
- 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.
