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Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization

2016; Elsevier BV; Volume: 155; Linguagem: Inglês

10.1016/j.lfs.2016.05.001

1879-0631

Samantha Climaco-Arvizu, Omar Domínguez-Acosta, María Asunción Cabañas-Cortés, Miriam Rodrı́guez-Sosa, Frank J. Gonzalez, Libia Vega, Guillermo Elizondo,

Per- and polyfluoroalkyl substances research

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of environmental pollutants. It is also implicated in the regulation of the immune system. Ahr-null macrophages overproduce several proinflammatory cytokines following LPS-mediated stimulation, suggesting that AHR affects the balance between the inflammatory M1 and anti-inflammatory M2 phenotypes. Therefore, the present study aimed to examine whether the loss of AHR modifies macrophage polarization. Peritoneal macrophages from wild-type and Ahr-null mice were differentiated into M1 or M2 phenotype by treatment with LPS/IFNγ or IL-4, and several M1 and M2 markers were determined by qPCR and ELISA assays. Macrophage phagocytic capacity was determined through phagocytosis of yeast and Leishmania major infection assays. Nitric oxide (NO) and urea production, and arginase activity were also determined. When macrophages were polarized to the M1 phenotype, Ahr-null cells presented a mixed response; higher levels of IL-1β, IL-6, IL-12, and TNFα were observed after IFNγ- and LPS-mediated activation. However, Ahr-null cells also exhibited decreased NO production and phagocytic capacity. When macrophage was polarized to the M2 phenotype, Ahr-null cells exhibited lower levels of Fizz1, Ym1, and IL-10. In contrast, arginase activity was increased when compared to wild-type macrophages. In addition, macrophages from Ahr-null mice were more susceptible to L. major infection. Disruption of the Ahr gene alters macrophage polarization when compared to WT macrophage. These changes may affect the development and resolution of several diseases such as bacterial or parasitic infections.