Doxycycline reduces the inflammatory response of LPS-treated microglial cells

SOCIAS, SERGIO BENJAMIN; OUIDJA O.; SANTA CECILIA, FLAVIA; SEPULVEDA DIAZ, J.; CUNHA, THIAGO; DEL-BEL, ELAINE; HUNOT, S.; MICHEL, PATRICK; RAISMAN VOZARI R.

Washington

Congreso; Neuroscience 2014; 2014

Society for Neuroscience (EEUU)

We previously demonstrated that the antibacterial drug doxycycline confers neuroprotection in a Parkinson disease mouse model by restraining glial cell activation (Lazzarini et al, Glia, 2013). In the present study, we wished to explore further the potential of doxycycline against neuroinflammation, using microglial cell-enriched cultures prepared from post-natal (P1) mouse brain. More specifically, we evaluated the impact that a 4 hour pretreatment with doxycycline exerts on microglial cells exposed for the next 24 hours to the bacterial inflammogen LPS (1 ng/ml). Our results show that the calciumbinding protein Iba-1 used as a marker of microglial cell activation, was detectable in 80% Mac-1+ cells after LPS treatment and that this number dropped to 20% with an optimal concentration of doxycycline, i.e., 200μM. Coherent with this result, doxycycline diminished the release of two pro-inflammatory cytokines, TNFalpha and IL-1B and that of nitric oxide, a gaseous mediator of neuroinflammatory responses. Finally, doxycycline was also found highly effective in a situation where microglial cells were exposed to 10 ng/ml LPS, i.e., a concentration of the inflammogen required to adequately stimulate the production reactive oxygen species in microglial cells. Taken together our results suggest that doxycycline could operate as an efficient protective agent through a repressive effect on microglial cells.