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Title: Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK
Authors: Nassif, Rana M 
Chalhoub, Elias
Chedid, Pia
Hurtado-Nedelec, Margarita
Raya, Elia
Dang, Pham My-Chan
Marie, Jean-Claude
El-Benna, Jamel
Affiliations: Faculty of Health Sciences 
Keywords: AMPK
NADPH oxidase
Issue Date: 2022-01-29
Publisher: National Library of Medicine
Part of: Biomedicines
Volume: 10
Issue: 2
Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.
ISSN: 2227-9059
DOI: 10.3390/biomedicines10020319
Open URL: Link to full text
Type: Journal Article
Appears in Collections:Department of Medical Laboratory Sciences

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