| First Author | Tian J | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 12 | Pages | 4202-4213 |
| PubMed ID | 27630169 | Mgi Jnum | J:267793 |
| Mgi Id | MGI:6267922 | Doi | 10.1096/fj.201600392RR |
| Citation | Tian J, et al. (2016) Galectin-3 regulates inflammasome activation in cholestatic liver injury. FASEB J 30(12):4202-4213 |
| abstractText | Macrophage activation is an important feature of primary biliary cholangitis (PBC) pathogenesis and other cholestatic liver diseases. Galectin-3 (Gal3), a pleiotropic lectin, is produced by monocytic cells and macrophages. However, its role in PBC has not been addressed. We hypothesized that Gal3 is a key to induce NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in macrophages and in turn to propagate proinflammatory IL-17 signaling. In liver tissues from patients with PBC and dnTGF-betaRII mice, a model of autoimmune cholangitis, the expression of Gal3, NLRP3, and the adaptor protein adaptor apoptosis-associated speck-like protein was induced, with the downstream activation of caspase-1 and IL-1beta. In wild-type hepatic macrophages, deoxycholic acid induced the association of Gal3 and NLRP3 with direct activation of the inflammasome, resulting in an increase in IL-1beta. Downstream retinoid-related orphan receptor C mRNA, IL-17A, and IL-17F were induced. In Gal3(-/-) macrophages, no inflammasome activation was detected. To confirm the key role of Gal3 in the pathogenesis of cholestatic liver injury, we generated dnTGF-betaRII/galectin-3(-/-) (dn/Gal3(-/-)) mice, which showed impaired inflammasome activation along with significantly improved inflammation and fibrosis. Taken together, our data point to a novel role of Gal3 as an initiator of inflammatory signaling in autoimmune cholangitis, mediating the activation of NLRP3 inflammasome and inducing IL-17 proinflammatory cascades. These studies provide a rationale to target Gal3 in autoimmune cholangitis and potentially other cholestatic diseases.-Tian, J., Yang, G., Chen, H.-Y., Hsu, D. K., Tomilov, A., Olson, K. A., Dehnad, A., Fish, S. R., Cortopassi, G., Zhao, B., Liu, F.-T., Gershwin, M. E., Torok, N. J., Jiang, J. X. Galectin-3 regulates inflammasome activation in cholestatic liver injury. |
