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

Year: 2015

Type: article

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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2015.02.012

Institutions: Lund University, Karolinska Institutet, Science for Life Laboratory, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Karolinska University Hospital, Skåne University Hospital

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620

Funders: Gyllenstiernska Krapperupsstiftelsen, Galecto, National Stroke Foundation, Cancerfonden, Lunds Universitet, Karolinska Institutet, Vetenskapsrådet, Stiftelsen Lars Hiertas Minne, Kungliga Fysiografiska Sällskapet i Lund, Parkinsonfonden

Award: Brain inflammation following stroke and cardiac arrest -Restraining neuroinflammation and subsequent psychiatric disorders

OpenAlex ID: W1978655989