| First Author | Jeon SB | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 11 | Pages | 7037-46 |
| PubMed ID | 20980634 | Mgi Jnum | J:166149 |
| Mgi Id | MGI:4839839 | Doi | 10.4049/jimmunol.1000154 |
| Citation | Jeon SB, et al. (2010) Galectin-3 Exerts Cytokine-Like Regulatory Actions through the JAK-STAT Pathway. J Immunol 185(11):7037-46 |
| abstractText | Galectin-3, a beta-galactoside-binding lectin, has been proposed to have multifaceted functions in various pathophysiological conditions. However, the characteristics of galectin-3 and its molecular mechanisms of action are still largely unknown. In this study, we show that galectin-3 exerts cytokine-like regulatory actions in rat and mouse brain-resident immune cells. Both the expression of galectin-3 and its secretion into the extracellular compartment were significantly enhanced in glia under IFN-gamma-stimulated, inflamed conditions. After exposure to galectin-3, glial cells produced high levels of proinflammatory mediators and exhibited activated properties. Notably, within minutes after exposure to galectin-3, JAK2 and STAT1, STAT3, and STAT5 showed considerable enhancement of tyrosine phosphorylation; thereafter, downstream events of STAT signaling were also significantly enhanced. Treatment of the cells with pharmacological inhibitors of JAK2 reduced the galectin-3-stimulated increases of inflammatory mediators. Using IFN-gamma receptor 1-deficient mice, we further found that IFN-gammaR 1 might be required for galectin-3-dependent activation of the JAK-STAT cascade. However, galectin-3 significantly induced phosphorylation of STATs in glial cells from IFN-gamma-deficient mice, suggesting that IFN-gamma does not mediate activation of STATs. Collectively, our findings suggest that galectin-3 acts as an endogenous danger signaling molecule under pathological conditions in the brain, providing a potential explanation for the molecular basis of galectin-3-associated pathological events. |
