FGL2 regulates IKK/NF-κB signaling in intestinal epithelial cells and lamina propria dendritic cells to attenuate dextran sulfate sodium-induced colitis

Publication date: January 2020Source: Molecular Immunology, Volume 117Author(s): Tang Li, Ru-ru Chen, Hong-peng Gong, Bin-feng Wang, Xi-xi Wu, Yue-qiu Chen, Zhi-ming HuangAbstractInflammatory bowel disease (IBD) is an autoimmune disease characterized by an abnormal immune response. Fibrinogen-like protein 2 (FGL2) is known to have immunoregulatory and anti-inflammatory activity. The level of FGL2 is elevated in patients with IBD; however, its comprehensive function in IBD is almost unknown. In our study, we explored the effect of FGL2 on dextran sulfate sodium (DSS)-induced colitis in mice and on NF-κB signaling in intestinal epithelial cells (IECs) and lamina propria dendritic cells (LPDCs). We founded that FGL2−/− mice in the colitis model showed more severe colitis manifestations than WT mice did, including weight loss, disease activity index (DAI), and colon histological scores. FGL2−/− mice treated with DSS produced more proinflammatory cytokines (IL-1β, IL-6, TNF-α) in serum than WT mice did and demonstrated upregulated expression of TNF-α and inflammatory marker enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) in the colon tissue. Our data suggested that DSS-treated FGL2−/− mice showed stronger activation of NF-κB signaling, especially in IECs. Next, we demonstrated that recombinant FGL2 (rFGL2) inhibited the production of proinflammatory cytokines and the expression of inflammatory marker enzymes by downregulating the NF-κ...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research