| First Author | Li T | Year | 2020 |
| Journal | Mol Immunol | Volume | 117 |
| Pages | 84-93 | PubMed ID | 31743856 |
| Mgi Jnum | J:292647 | Mgi Id | MGI:6435605 |
| Doi | 10.1016/j.molimm.2019.11.001 | Citation | Li T, et al. (2020) FGL2 regulates IKK/NF-kappaB signaling in intestinal epithelial cells and lamina propria dendritic cells to attenuate dextran sulfate sodium-induced colitis. Mol Immunol 117:84-93 |
| abstractText | Inflammatory 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-kappaB 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-1beta, IL-6, TNF-alpha) in serum than WT mice did and demonstrated upregulated expression of TNF-alpha 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-kappaB 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-kappaB signaling in HT-29 cells. Finally, we discovered that LPDCs from the colon of DSS-treated FGL2(-/-) mice showed significantly upregulated expression of surface maturation co-stimulatory molecules, including CD80, CD86, CD40, and MHC class II molecules compared with that in WT mice. In addition, LPDCs in FGL2(-/-) treated with DSS exhibited excessive NF-kappaB activity and the administration of rFGL2 to FGL2(-/-) mice could rescue the aggravated results of FGL2(-/-) mice. Taken together, our findings demonstrated that FGL2 might be a target for further therapy of IBD. |
