Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways

FLAVIA V. SANTA-CECILIA; BENJAMIN SOCIAS; MOHAND O. OUIDJA; JULIA E. SEPULVEDA-DIAZ; LEONARDO ACUÑA; RANGEL L. SILVA; PATRICK P. MICHEL; ELAINE DEL-BEL; THIAGO M. CUNHA; RITA RAISMAN-VOZARI

NEUROTOXICITY RESEARCH

SPRINGER

Lugar: Berlin; Año: 2016

1029-8428

In neurodegenerative diseases, the inflammatoryresponse is mediated by activated glial cells, mainlymicroglia, which are the resident immune cells of thecentral nervous system. Activated microglial cells releaseproinflammatory mediators and neurotoxic factors that aresuspected to cause or exacerbate these diseases. Werecently demonstrated that doxycycline protects substantianigra dopaminergic neurons in an animal model ofParkinson?s disease. This effect was associated with areduction of microglial cell activation, which suggests thatdoxycycline may operate primarily as an anti-inflammatorydrug. In the present study, we assessed the anti-inflammatorypotential of doxycycline using lipopolysaccharide(LPS)-activated primary microglial cells in culture as amodel of neuroinflammation. Doxycycline attenuated theexpression of key activation markers in LPS-treatedmicroglial cultures in a concentration-dependent manner.More specifically, doxycycline treatment lowered theexpression of the microglial activation marker IBA-1 aswell as the production of ROS, NO, and proinflammatorycytokines (TNF-a and IL-1b). In primary microglial cells,we also found that doxycycline inhibits LPS-induced p38MAP kinase phosphorylation and NF-kB nuclear translocation.The present results indicate that the effect ofdoxycycline on LPS-induced microglial activation probablyoccurs via the modulation of p38 MAP kinase and NFkBsignaling pathways. These results support the idea thatdoxycycline may be useful in preventing or slowing theprogression of PD and other neurodegenerative diseasesthat exhibit altered glia function