Ruxolitinib Alleviates Inflammation, Apoptosis, and Intestinal Barrier Leakage in Ulcerative Colitis via STAT3

作者：Chunxiao Li, Yu Xu, Tengjiao Gao, Shunyao Zhang, Zhe Lin, Shaobo Gu, Fang Yi, Xin Yuan, Siyi Yu, Qi Jiang, Zhongze Lou, Xiuming Zhang, Jie Zhang, Qiaoyan Wu, Mengli Gu, Xiaoyun Ding, Jing Sun, Yi Chen · 发表于：Inflammatory Bowel Diseases · 年份：2023 · DOI：10.1093/ibd/izad007 · 被引用次数：19 · 研究领域：Inflammatory Bowel Disease、Cytokine Signaling Pathways and Interactions、Psoriasis: Treatment and Pathogenesis

BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa with increasing prevalence and limited management. Ruxolitinib is a new anti- JAK/STAT3 biologic agent that has shown potential in protecting against colitis. METHODS: We first constructed an in vivo UC model and an in vitro colonic epithelial cell inflammation model. Ruxolitinib was administered via gavage in mice. After treatment, colon tissues, cells, and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, immunofluorescence staining, quantitative reverse-transcriptase polymerase chain reaction, Western blotting, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining, and cytokine analysis. STAT3 expression was silenced and overexpressed via small interfering RNA and overexpression plasmid transfection, respectively, and quantitative reverse-transcriptase polymerase chain reaction was used to examine the downstream effects. RESULTS: Ruxolitinib administration significantly alleviated colitis both in vivo and in vitro, as manifested by reduced body weight loss, shortened colon lengths, relieved disease activity (measured by the disease activity index), and prolonged survival. A mechanistic study showed that ruxolitinib attenuated nuclear factor kappa B-induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage, and thereby reduced colitis activity in vivo. STAT3 knockdown partially r...