Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways

低剂量白细胞介素-2通过恢复肠道完整性和抑制AKT依赖性通路减轻小鼠葡聚糖硫酸钠诱发的结肠炎

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作者:Hana Lee, Ye Seul Son, Mi-Ok Lee, Jea-Woon Ryu, Kunhyang Park, Ohman Kwon, Kwang Bo Jung, Kwangho Kim, Tae Young Ryu, Aruem Baek, Janghwan Kim, Cho-Rok Jung, Choong-Min Ryu, Young-Jun Park, Tae-Su Han, Dae-Soo Kim, Hyun-Soo Cho, Mi-Young Son

Conclusions

The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC.

Methods

Mice with DSS-induced colitis were intraperitoneally injected with low-dose IL-2. Survival, body weight, disease activity index, colon length, histopathological score, myeloperoxidase activity and inflammatory cytokine levels as well as intestinal barrier integrity were examined. Differential gene expression after low-dose IL-2 treatment was analyzed by RNA-sequencing.

Results

Low-dose IL-2 significantly improved the symptoms of DSS-induced colitis in mice and attenuated pro-inflammatory cytokine production and immune cell infiltration. The most effective dose range of IL-2 was 16K-32K IU/day. Importantly, low-dose IL-2 was effective in ameliorating the disruption of epithelial barrier integrity in DSS-induced colitis tissues by restoring tight junction proteins and mucin production and suppressing apoptosis. The colon tissue of DSS-induced mice exposed to low-dose IL-2 mimic gene expression patterns in the colons of control mice. Furthermore, we identified the crucial role of the PI3K-AKT pathway in exerting the therapeutic effect of low-dose IL-2. Conclusions: The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC.

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