BMC Seminar - Role of TLR4

BMC Seminar Thursday September 5th, 12:00 in Læknagarður Vatnsmýrarvegur 16, room 201

Speaker: Professor María Pascual, Department of Physiology in the Faculty of Medicine and Dentistry, University of Valencia, Spain

Title: Extracellular vesicles participate in the effects of ethanol in the neuroinflammation: Role of TLR4

Abstract: Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signalling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Using EVs from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated with ethanol, we have demonstrated that ethanol increases the number of secreted nanovesicles and their content by raising the levels of both inflammatory-related proteins (TLR4, NFκB-p65, IL-1R, caspase-1, NLRP3) and by changing miRNAs (mir-146a, mir-182, and mir-200b) in the EVs from the WT-astrocytes compared with those from the untreated WT cells. No changes were observed between the untreated and ethanol-treated TLR4-KO astrocytes. We also show that astrocyte-derived EVs could be internalized by naïve cortical neurons to increase the neuronal levels of inflammatory protein (COX-2) and miRNAs (e.g., mir-146a) and to compromise their survival. These results suggest that astrocyte-derived EVs could act as cellular transmitters of inflammation signaling by spreading and amplifying the neuroinflammatory response induced by ethanol through TLR4 activation.

Biography: I have a PhD in Pharmacy by the University of Navarra (Pamplona, Spain). From 1999 to 2001 I was working as postdoctoral student in Consuelo Guerri’s laboratory at Principe Felipe Research Center in Valencia and then as a researcher in the same lab, where we have published numerous papers and book’s chapters associated with the activation of the inflammatory immune response induced by alcohol in glial cells and in developmental brain. Since 2009 and during 8 years, I was Associate professor in the Physiology Department at the University of Valencia, and actually I am Assistant professor in the same department.