title: Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.
abstract: Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.
authors.affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, Stockholm 171 76, Sweden; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden. Electronic address: m.burguillos@qmul.ac.uk.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Burguillos
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden.
authors.forename: Martina
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet, Stockholm 17165, Sweden.
authors.forename: Tim
authors.initials: T
authors.lastname: Schulte
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Boza-Serrano
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Garcia-Quintanilla
authors.affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, Stockholm 171 76, Sweden.
authors.forename: Edel
authors.initials: E
authors.lastname: Kavanagh
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
authors.forename: Martiniano
authors.initials: M
authors.lastname: Santiago
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
authors.forename: Nikenza
authors.initials: N
authors.lastname: Viceconte
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Oliva-Martin
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Q2:07, Stockholm 171 76, Sweden.
authors.forename: Ahmed Mohamed
authors.initials: AM
authors.lastname: Osman
authors.affiliation: Section MIG, Department of Laboratory Medicine, Solvegatan 23, Lund University, Lund 223 62, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Salomonsson
authors.affiliation: Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund 221 84, Sweden.
authors.forename: Lahouari
authors.initials: L
authors.lastname: Amar
authors.affiliation: Department of Pathology, Division of Neuropathology, Lund University Hospital, Lund 221 85, Sweden.
authors.forename: Annette
authors.initials: A
authors.lastname: Persson
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Q2:07, Stockholm 171 76, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.affiliation: Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet, Stockholm 17165, Sweden.
authors.forename: Adnane
authors.initials: A
authors.lastname: Achour
authors.affiliation: Department of Pathology, Division of Neuropathology, Lund University Hospital, Lund 221 85, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: Section MIG, Department of Laboratory Medicine, Solvegatan 23, Lund University, Lund 223 62, Sweden.
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Venero
authors.affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, Stockholm 171 76, Sweden.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Deierborg