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

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-1ß, 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.

Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers.

Inflammatory bowel disease (IBD) in humans is closely related to bacterial infection and the disruption of the intestinal barrier. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora Pallas plants, exerts a potential effect of anti-inflammatory reported in various researches. However, the effect of PF on intestinal barrier function and its related mechanisms has not been identified. Here, we investigate the PF potential anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated human Caco-2 cell monolayers and explore its underlying key molecular mechanism. In this context, PF significantly increased TEER value, decreased intestinal epithelium FITC-dextran flux permeability, and restored the expressions of occludin, ZO-1, and claudin5 in LPS-induced Caco-2 cell. In vitro, treatment of PF significantly inhibited LPS-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). In addition, we found that PF suppressed nuclear factor kappa B (NF-κB) signaling via activating the Nrf2/HO-1 signaling pathways in ILPS-stimulated Caco-2 cells. Our findings indicate that PF has an inhibitory effect on endothelial injury. Our findings suggested that PF has an anti-inflammatory effect in ILPS-stimulated Caco-2 cells, which might be a potential therapeutic agent against IBD and intestinal inflammation.

Peripapillary choroidal thickness in Chinese children using enhanced depth imaging optical coherence tomography.

AIM: To evaluate the peripapillary choroidal thickness (PPCT) in Chinese children, and to analyze the influencing factors. METHODS: PPCT was measured with enhanced depth imaging optical coherence tomography (EDI-OCT) in 70 children (53 myopes and 17 non-myopes) aged 7 to 18y, with spherical equivalent refractive errors between 0.50 and -5.87 diopters (D). Peripapillary choroidal imaging was performed using circular scans of a diameter of 3.4 mm around the optic disc. PPCT was measured by EDI-OCT in six sectors: nasal (N), superonasal (SN), superotemporal (ST), temporal (T), inferotemporal (IT) and inferonasal (IN), as well as global RNFL thickness (G). RESULTS: The mean global PPCT was 165.49±33.76 µm. The temporal, inferonasal, inferotemporal PPCT were significantly thinner than the nasal, superonasal, superotemporal segments PPCT were significantly thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was significantly associated with the average global (ß=-0.419, P=0.014), superonasal (ß=-2.009, P=0.049) and inferonasal (ß= -2.000, P=0.049) PPCT. The other factors (gender, age, SE) were not significantly associated with PPCT. CONCLUSION: PPCT was thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was found to be negatively correlated to PPCT. We need more further studies about the relationship between PPCT and myopia.