Therapeutic effect of anti-CXCL1 neutralizing antibody on acute ulcerative colitis in mice

Abstract

To evaluate the therapeutic effect of CXCL1 monoclonal antibody on dextra sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice, and to elucidate its effect on the expressions of TNF-α, IFN-γ, IL-17 and IL-10 as well as neutrophil infiltration. Methods: Female BALB/c mice were randomly divided into a normal group (DSS-), a disease group (DSS+saline), an anti-CXCL1 antibody group (DSS+anti-CXCL1 Ab) and a treatment control group (DSS+IgG Ab). The DSS+saline, DSS+anti-CXCL1 Ab and DSS+anti-CXCL1 Ab groups were given 3.5% DSS solution as drinking water to induce acute intestinal inflammation, while the normal control was given distilled water freely. The DSS+anti-CXCL1 Ab mice were intraperitoneal injected with anti-CXCL1 Ab (4 mg/kg) on the 3rd and 6th day. Same amount of rat IgG Ab was given in the DSS+IgG Ab group. The normal group and the disease group were injected with 0.9% sodium chloride solution. The value of disease activity index (DAI) and the injury of colorectal tissue were measured. The levels of TNF-α, IFN-γ, IL-10 and IL-17 in colonic tissues of mice were detected by RT-PCR. Myeloperoxidase (MPO), a specific marker of neutrophils was measured by immunohistochemistry. Results: Compared with the normal control group, DAI score and colorectal injury score in the disease group were significantly increased, but the DAI and colorectal in the mice with acute ulcerative colitis tissue damage score were significantly reduced after anti-CXCL1 Ab intervention. Compared with the normal control group, mRNA levels of TNF-α, IFN-γ and IL-17 in the colorectal tissues were significantly elevated (P<0.05) in the disease group while the IL-10 was decreased; these effects were attenuated by anti-CXCL1 Ab intervention (P<0.05). Immunohistochemistry showed that the infiltration of neutrophils (MPO+) in the colon tissue was significantly increased in the disease group, while the anti-CXCL1 Ab treatment could significantly reduce the neutrophil infiltration in colon tissue (P<0.05). Conclusion: Anti-CXCL1 Ab relieves the progression of DSS-induced acute ulcerative colitis by suppressing proinflammatory expression and neutrophil infiltration.