Treatment with sitagliptin exacerbates the M2 phenotype in macrophages in vitro

Autor(es)

Quadros-Pereira, Laura ; Nery-Neto, Jose Arimatea de Oliveira ; Da Silva, Eloisa Martins ; Doretto-Silva, Lorena ; Yariwake, Victor Yuji ; Camara, Niels Olsen ; Andrade-Oliveira, Vinicius

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 145, p. 13-pg., 2024-12-10.

Resumo

Macrophages (M & Oslash;) participate in the induction and the control of the host's immune response in homeostasis and during inflammatory diseases. Sitagliptin is a drug that inhibits the enzyme dipeptidyl peptidase 4 (DPP-4) and, therefore, increases the bioavailability of the incretins GIP (Gastric inhibitory polypeptide) and GLP-1 (Glucagonlike polypeptide). Thus, sitagliptin has been used to treat obesity and type II diabetes and has recently been associated with anti-inflammatory effects. It is known that the drug can modulate the immune response, however, the underlying mechanisms are not yet completely elucidated, including how they interfere with the activation and function of M & Oslash;. Here, we aimed to investigate and characterize the effects of in vitro treatment with sitagliptin on M & Oslash; polarization. Bone marrow-derived M & Oslash; were differentiated with conditioned medium from the L929 cell line. For M1, M & Oslash; were stimulated with IFN-gamma and LPS, and for M2, with IL-4 and IL-13 for 24 h. Sitagliptin treatment was performed during M & Oslash; polarization. Polarized M & Oslash; were assessed for M1/M2 markers, DPP-4, GLP-1 and GIP receptors, mitochondrial dynamics and phagocytosis. Sitagliptin treatment exacerbates the M2 phenotype, featured by increased expression of CD206 and ARG1 and decreased gene expression levels of TNF-alpha. Sitagliptin-treated M2 altered mitochondrial dynamics with reduced membrane potential and mitochondrial reactive oxygen species production. These differences were accompanied by low gene expression levels of genes related to mitofusion, suggesting that sitagliptin treatment interferes with mitochondria function in M2, and exhibited less phagocytic capacity. In summary, our data suggest that sitagliptin exacerbates M2 profile in vitro. (AU)

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