Doxycycline suppresses microglia activation by inhibiting the p38 MAPK and NFkB signaling pathways

SOCIAS, SERGIO BENJAMIN; SANTA CECILIA, FLAVIA; OUIDJA O.; SEPULVEDA DIAZ, J.; MICHEL, PATRICK; DEL-BEL, ELAINE; CUNHA, THIAGO; RASIMAN-VOZARI, RITA

NEUROTOXICITY RESEARCH

SPRINGER

Lugar: Berlin; Año: 2016 vol. 29 p. 447 - 459

1029-8428

In neurodegenerative diseases, the inflammatory response is principally mediated by activated glial cells, mainly microglia, the resident immune cells of the CNS. Stimulated microglial cells release proinflammatory molecules and neurotoxic factors that are suspected to cause or exacerbate these diseases. We demonstrated recently that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson?s disease. This effect was associated with a reduction of microglial cell activation which suggests that doxycycline may operate primarily as an antiinflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using a model system of microglial cells in culture. Doxycycline was able to restrain Lipopolysaccharide (LPS)-induced activation of microglial cells, in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the ionized calcium-binding adapter molecule 1 (IBA-1), the production of cytokines such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1B) and that of nitric oxide (NO) and reactive oxygen species (ROS). We also found that doxycycline treatment inhibits LPS-induced activation of p38 MAP kinase and NF-kB signaling pathways. Overall, the present results indicate that doxycycline may operate by suppressing microglial cell activation, an effect possibly mediated through inhibition of p38 MAP kinase and NF-kB-dependent signaling pathways. In conclusion, the present data support the idea that doxycycline has therapeutic potential for treating Parkinson?s disease.