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-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-κB 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-κB 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.

中文翻译：

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FGL2调节肠上皮细胞和固有层树突状细胞中的IKK /NF-κB信号传导，以减轻硫酸葡聚糖钠诱导的结肠炎。

炎性肠病（IBD）是一种以异常免疫反应为特征的自身免疫性疾病。已知纤维蛋白原样蛋白2（FGL2）具有免疫调节和抗炎活性。IBD患者的FGL2水平升高；然而，其在IBD中的全面功能几乎是未知的。在我们的研究中，我们探讨了FGL2对小鼠右旋糖酐硫酸钠（DSS）引起的结肠炎以及肠上皮细胞（IECs）和固有层树突状细胞（LPDC）中NF-κB信号传导的影响。我们发现，结肠炎模型中的FGL2-/-小鼠比野生型小鼠表现出更严重的结肠炎表现，包括体重减轻，疾病活动指数（DAI）和结肠组织学评分。用DSS处理的FGL2-/-小鼠产生更多的促炎细胞因子（IL-1β，IL-6，与野生型小鼠相比，血清中的TNF-α含量更高，并证明了结肠组织中TNF-α和炎性标记酶，诱导型一氧化氮合酶（iNOS）和环氧合酶2（Cox-2）的表达上调。我们的数据表明，经DSS处理的FGL2-/-小鼠显示出更强的NF-κB信号激活，特别是在IEC中。接下来，我们证明了重组FGL2（rFGL2）通过下调HT-29细胞中的NF-κB信号传导来抑制促炎细胞因子的产生和炎症标记酶的表达。最后，我们发现，DSS处理的FGL2-/-小鼠结肠中的LPDC与WT小鼠相比，表面成熟共刺激分子（包括CD80，CD86，CD40和MHC II类分子）的表达明显上调。此外，用DSS处理的FGL2-/-中的LPDC表现出过高的NF-κB活性，向FGL2-/-小鼠施用rFGL2可以挽救FGL2-/-小鼠的恶化结果。综上所述，我们的发现表明FGL2可能是IBD进一步治疗的目标。