Insulin Antagonizes LPS-Induced Inflammatory Responses by Activating SR-A1/ERK Axis in Macrophages.

Insulin is a key regulator of metabolism and inflammation in the body. However, the mechanism of the anti-inflammatory effect of insulin is not fully understood. In the present study, we investigated the role of the class A1 scavenger receptor (SR-A1), a prototypic member of the pattern recognition receptor family, in the insulin-mediated suppression of inflammatory responses in macrophages. Our murine in vivo studies show that insulin can attenuate lipopolysaccharide (LPS)-induced endotoxemia in a SR-A1-dependent manner, and this was consistent with our in vitro results which demonstrate that the SR-A1 is necessary for insulin to antagonize the LPS-induced inflammatory responses in macrophages. The effect of SR-A1 on the anti-inflammatory action of insulin might be associated with the activation of the extracellular signal-regulated kinases (ERK) signaling pathway in macrophages. Insulin could inhibit macrophage polarization to a pro-inflammatory phenotype via the SR-A1/ERK cascade. Collectively, our results suggest that SR-A1 may be a pivotal element for the anti-inflammation effect of insulin in macrophages.