Glutathione S-transferases promote proinflammatory astrocyte-microglia communication during brain inflammation

Astrocytes and microglia play critical roles in brain inflammation. Here, we report that glutathione S-transferases (GSTs), particularly GSTM1, promote proinflammatory signaling in astrocytes and contribute to astrocyte-mediated microglia activation during brain inflammation. In vivo, astrocyte-specific knockdown of GSTM1 in the prefrontal cortex attenuated microglia activation in brain inflammation induced by systemic injection of lipopolysaccharides (LPS). Knocking down GSTM1 in astrocytes also attenuated LPS-induced production of the proinflammatory cytokine tumor necrosis factor–α (TNF-α) by microglia when the two cell types were cocultured. In astrocytes, GSTM1 was required for the activation of nuclear factor B (NF-B) and the production of proinflammatory mediators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and C-C motif chemokine ligand 2 (CCL2), both of which enhance microglia activation. Our study suggests that GSTs play a proinflammatory role in priming astrocytes and enhancing microglia activation in a microglia-astrocyte positive feedback loop during brain inflammation.

Source: Signal Transduction Knowledge Environment - February 19, 2019 Category: Science Authors: Kano, S.-i., Choi, E. Y., Dohi, E., Agarwal, S., Chang, D. J., Wilson, A. M., Lo, B. D., Rose, I. V. L., Gonzalez, S., Imai, T., Sawa, A. Tags: STKE Research Articles Source Type: news