Salvianolic acid B decreases interleukin-1ß-induced colitis recurrence in mice.

BACKGROUND: Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS: Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1ß (IL-1ß) was injected intraperitoneally to induce colitis recurrence. RESULTS: Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ±â€Š3.46% to 162.89 ±â€Š11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ±â€Š9.29% to 296.23 ±â€Š30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ±â€Š8.45% vs. 162.89 ±â€Š11.45%, P = 0.0059) and Sal B (104.27 ±â€Š6.09% vs. 162.89 ±â€Š11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ±â€Š89.42% vs. 296.23 ±â€Š30.78%, P = 0.0028) but not influenced by SASP (285.23 ±â€Š41.04% vs. 296.23 ±â€Š30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1ß in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS: These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Expression of IARS2 gene in colon cancer and effect of its knockdown on biological behavior of RKO cells.

OBJECTIVE: To investigate the expression level of IARS2 gene in colon cancer tissues and various cell strains of the cancer; to explore cytologically the effect of IARS2 gene knockdown on proliferation, apoptosis and cell cycle of RKO cells in the cancer. METHODS: Real-time, fluorescence-based quantitative PCR (qPCR) was used to detect the expression of IARS2 gene in human colon cancer and surrounding tissues and in various cell strains of the cancer; the RNA interference target of IARS2 gene was designed and the target was detected by Western blot; the IARS2-siRNA lentiviral vector was established and used to infect the RKO cells of colon cancer; qPCR was employed to determine the effect of gene knockdown; changes of the RKO cells in growth, apoptosis, cell cycle and clone formation were observed after IARS2 gene knockdown. RESULTS: The expression of IARS2 gene was higher in human colon cancer tissues than in surrounding tissues; there was expression of IARS2 gene in colon cancer cells, and the expression level of IARS2 gene mRNA was higher in the RKO cells than in the SW480, HCT116, DLD1, HT-29 and SW620 cells. After infection of the RKO cells with IARS2-siRNA lentivirus, the expression of IARS2 gene was inhibited in the level of mRNA; proliferation rate of the RKO cells was significantly inhibited; the G1 phase arrest of the RKO cells was increased with less RKO cells in S phase; the apoptotic RKO cells increased significantly; and the number of colonies of the RKO cells reduced. CONCLUSION: The expression of IARS2 gene is different in human colon cancer and surrounding tissues; after knockdown of IARS2 gene, proliferation of the RKO cells is inhibited; there are more cells in G phase and fewer cells in S phase; apoptosis of cells is increased; and formation of colonies is reduced. IARS2 gene is probably a cancer-promoting gene.