Details

Autor(en) / Beteiligte

• Burguillos, Miguel Angel
• Svensson, Martina
• Schulte, Tim
• Boza-Serrano, Antonio
• Garcia-Quintanilla, Albert
• Kavanagh, Edel
• Santiago, Martiniano
• Viceconte, Nikenza
• Oliva-Martin, Maria Jose
• Osman, Ahmed Mohamed
• Salomonsson, Emma
• Amar, Lahouari
• Persson, Annette
• Blomgren, Klas
• Achour, Adnane
• Englund, Elisabet
• Leffler, Hakon
• Venero, Jose Luis
• Joseph, Bertrand
• Deierborg, Tomas

Titel

Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

Ist Teil von

• Cell reports (Cambridge), 2015-03, Vol.10 (9), p.1626-1638

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Gal3 acts as an endogenous TLR4 ligand with a Kd value around 1 μM•Gal3 can initiate a TLR4-dependent inflammatory response in microglia•Gal3 is required for complete activation of TLR4 upon LPS treatment•Gal3-TLR4 interaction is confirmed in vivo and in stroke patients In this publication, Burguillos et al. demonstrate how galectin-3 (Gal3) released from reactive microglia cells can activate other surrounding immune cells in a paracrine manner by binding to and activating Toll-like receptor 4 (TLR4). This finding could explain the propagation of the inflammatory response once the initial stimulus is gone.