CCL2 Inhibition of Pro-Resolving Mediators Potentiates Neuroinflammation in Astrocytes



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Gutiérrez Cañas, Irene and Novellino, Fabiana and Caso Fernández, Javier Rubén and García Bueno, Borja and Leza Cerro, Juan Carlos and Muñoz Madrigal, José Luis (2022) CCL2 Inhibition of Pro-Resolving Mediators Potentiates Neuroinflammation in Astrocytes. International Journal of Molecular Sciences, 23 (6). p. 3307. ISSN 1422-0067

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The chemokine CCL2 participates in multiple neuroinflammatory processes, mainly through the recruitment of glial cells. However, CCL2 has also been proven to exert different types of actions on these cells, including the modification of their response to inflammatory stimuli. In the present study we analyzed the effect of CCL2 on the resolution of inflammation in astrocytes. We observed that genetic removal of CCL2 increases the expression of the enzymes responsible for the synthesis of specialized pro-resolving mediators arachidonate 15-lipoxygenase and arachidonate 5-lipoxygenase in the brain cortex of 5xFAD mice. The expression of FPR2 receptor, known to mediate the activity of pro-resolving mediators was also increased in mice lacking CCL2.The downregulation of these proteins by CCL2 was also observed in cultured astrocytes. This suggests that CCL2 inhibition of the resolution of inflammation could facilitate the progression of neuroinflammatory processes. The production of the pro-inflammatory cytokine IL-1beta by astrocytes was analyzed, and allowed us to confirm that CCL2 potentiates the activation of astrocytes trough the inhibition of pro-resolving pathways mediated by Resolvin D1. In addition, the analysis of the expression of TNFalpha, MIP1alpha and NOS2 further confirmed CCL2 inhibition of inflammation resolution in astrocytes.

Item Type:Article
Uncontrolled Keywords:CCL2; MCP-1; resolvin; LPS; astrocytes; inflammation
Subjects:Medical sciences > Medicine > Pharmacology
Medical sciences > Medicine > Neurosciences
ID Code:73370
Deposited On:06 Jul 2022 14:56
Last Modified:07 Jul 2022 07:11

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