Therapeutic Effect And Mechanisms Of IL-15 Mutant/Fc?2a Fusion Protein In Mice With Ulcerative Colitis

Objective:To investigate the therapeutic effect and mechanisms of IL-15 mutant/Fcy2a fusion protein(IL-15 mutant/Fc) in mice with ulcerative colitis and explore the possible mechanism from the perspective of AKT and STAT signaling pathway.Methods:Thirty BALB/c mice were randomly divided into control group, IL-15 mutant/Fc treatment group and IgG2a treatment group. Ulcerative colitis model was induced in the latter two groups by continuous drinking of 5% dextran sulphate sodium in water for 7 days. Each mouse in IL-15 mutant/Fc treatment group was injected with IL-15 mutant/Fc(5?g/100?l) intraperitoneally every day for 7 consecutive days, Each mouse in IgG2a treatment group was injected with IgG2a (5?g/100?l) intraperitoneally every day for 7 consecutive days.During the experimental period, the general condition, weight, colon macroscopic pathologic score were used to evaluate the protective effects. Hematoxylin-eosin(HE) staining of the distal colon mucosa of mice in each group was taken to study the histopathological injury and histological score. ELISA assay was taken to measure the content of inflammatory cytokines(IL-10, IL-15, TNF-a) in ocular blood of mice. Expression of STAT3 and STAT5 mRNA were detected by reverse transcriptase polymerase chain reaction(RT-PCR), and expression of p-STAT5 and p-AKT protein were assessed by Western Blot.Results:Compared with control group, mice in the other two groups showed poor general conditions and changes in body weight, while the general conditions and histopathological score of mice in IL-15 mutant/Fc treatment group were better than those in IgG2a treatment group. The secretion disorder of pro-inflammatory cytokines and anti-inflammatory cytokine could be partially alleviated by injection of IL-15mutant/Fc demonstrated by increase of IL-10 and decrease of IL-15 and TNF-?. The levels of STAT3?STAT5 mRNA and p-STAT5?p-AKT protein of IL-15 mutant/Fc treatment group were obviously lower than those of IgG2a treatment group(p<0.05).Conclusion:As a specific IL-15 receptor antagonist, IL-15 mutant/Fc can achieve its therapeutic effect to ameliorate UC by intervening the signaling pathway through regulating the mRNA or protein expressions of key signal molecules, such as STAT and AKT.