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
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.
Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden.
Cell Rep. 2015 Mar 10;10(9):1626-1638. doi: 10.1016/j.celrep.2015.02.012. Epub 2015 Mar 5.
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.
小胶质细胞诱导的炎症反应在神经炎症性疾病中神经元群体的死亡中起关键作用。尽管Toll样受体4（TLR4）在小胶质细胞炎症反应中的作用已得到充分认可，但对于触发TLR4激活的内源性配体却知之甚少。在此，我们报告小胶质细胞释放的半乳糖凝集素-3（Gal3）作为内源性旁分泌TLR4配体。Gal3与TLR4的相互作用在小鼠神经炎症模型（黑质内注射脂多糖[LPS]）和人类中风受试者中得到进一步证实。在全脑缺血后以及在神经炎症性LPS模型中，Gal3的缺失发挥了神经保护和抗炎作用。这些结果表明，Gal3依赖性TLR4激活可能导致小胶质细胞持续激活，延长大脑中的炎症反应。
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