Metformin Attenuates Production of Nitric Oxide in Response to Lipopolysaccharide by Inhibiting MyD88-Independent Pathway

Abstract

Metformin is reported to ameliorate inflammation in diabetic patients. The effect of metformin on lipopolysaccharide-induced nitric oxide production was studied by using RAW 264.7 macrophage-like cells. The action of metformin was analyzed by dividing lipopolysaccharide signaling into the MyD88-dependent and -independent pathways. Metformin significantly reduced the expression of an inducible type of nitric oxide synthase and inhibited lipopolysaccharide-induced nitric oxide production. On the other hand, metformin did not inhibit lipopolysaccharide-induced tumor necrosis factor-α production. The expression levels of interferon-β protein and mRNA, which is a key molecule in MyD88-independent pathway, were significantly inhibited by metformin. Compound C, a specific AMP-activated protein kinase inhibitor, did not affect the inhibitory action of metformin. Metformin was suggested to inhibit lipopolysaccharide-induced nitric oxide production via inhibition of interferon-β production in MyD88-independent pathway. Metformin might exhibit an anti- inflammatory action on diabetic complications as well as the antidiabetic action.

lipopolysaccharide - interferon-β - metformin - MyD88-independent pathway - nitric oxide

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