Metformin Suppresses LPS-Induced Inflammatory Responses in Macrophage and Ameliorates Allergic Contact Dermatitis in Mice via Autophagy

Allergic contact dermatitis (ACD) is one of the most common skin diseases caused by hapten-modified proteins. Metformin, a drug commonly prescribed for type II diabetes, has been demonstrated to have various biological functions beyond its antidiabetic effects. However, its role in ACD remains unknown. In the present study, we found that metformin reduced the production of nitric oxide (NO) and the level of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. These anti-inflammatory effects were also demonstrated on bone marrow-derived macrophages (BMDMs). Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells. Besides, metformin attenuated 2,4-dinitrofluorobenzene (DNFB)-induced ACD and inhibited proinflammatory cytokines in the ear. In addition, metformin ameliorated ACD partly through the inhibition of macrophage activation and the induction of autophagic flux. Taken together, our data indicated that metformin ameliorates ACD through enhanced autophagic flux to inhibit macrophage activation and provides a potential contribution to ACD treatment.