Previous studies have shown that TLR4/NF-KB pathway is involved in the occurrence and development of ulcerative colitis (UC), and IL-1 receptor associated kinase1/4(IRAK1/4) are two main kinases of this pathway, which have a positive regulatory effect. IRAK1/4 inhibitors have been clinically tested in rheumatic diseases, hematological diseases and other diseases, but have not been studied in UC. Researchers from the Renmin Hospital of Wuhan University aimed to explore the pharmacological effects of IRAK1/4 inhibitor I on experimental colitis in mice and discuss the underlying mechanisms.
In this study, experimental colitis was induced in mice using 3% dextran sulfate sodium (DSS). By detecting the expression of TLR4/NF-KB pathway and intestinal barrier related proteins, the level of inflammatory factors and intestinal permeability were identified to evaluate the degree of intestinal injury.
Researchers found that IRAK1/4 inhibitor I can significantly relieve the symptoms of colitis in mice, alleviate intestinal pathological damage, reduce the level of inflammatory factors, reduce intestinal permeability, and protect the intestinal barrier function. Results showed that IRAK1/4 inhibitor I can effectively treat mouse colitis, providing a certain basic research reference for the application of IRAK 1/4 inhibitor I in the clinical treatment of UC in the future.
既往研究表明，TLR4/NF-κB通路參與潰瘍性結腸炎（UC）的發生和發展，IL-1受體相關激酶1/4（IRAK1/4）是該通路的兩個主要激酶，具有積極的調節作用。 IRAK1/4 抑製劑已在風濕病、血液病等疾病中進行了臨床試驗，但尚未在 UC 中進行研究。武漢大學人民醫院的研究人員旨在探索 IRAK1/4 抑製劑 I 對小鼠實驗性結腸炎的藥理作用，並討論其潛在機制。
在這項研究中，使用 3% 葡聚醣硫酸鈉 (DSS) 在小鼠中誘導了實驗性結腸炎。通過檢測TLR4/NF-κB通路和腸屏障相關蛋白的表達，鑑定炎症因子水平和腸道通透性，以評估腸道損傷程度。
研究人員發現，IRAK1/4 inhibitor I可以顯著緩解小鼠結腸炎症狀，減輕腸道病理損傷，降低炎症因子水平，降低腸道通透性，保護腸道屏障功能。結果表明，IRAK1/4 inhibitor I可以有效治療小鼠結腸炎，為未來IRAK 1/4 inhibitor I在UC臨床治療中的應用提供一定的基礎研究參考。
Reference: Yan B, Li X, Zhou L, Qiao Y, Wu J, Zha L, Liu P, Peng S, Wu B, Yu X, Shen L. Inhibition of IRAK 1/4 alleviates colitis by inhibiting TLR4/ NF-κB pathway and protecting the intestinal barrier. Bosn J of Basic Med Sci [Internet]. 2022Jun.13 [cited 2022Oct.12];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7348
Editor: Merima Bukva, MPharm