Khan Md Rafiqul Islam, Uwada Junsuke, Yazawa Takashi, Islam Md Tariqul, Krug Susanne M, Fromm Michael, Karaki Shin-ichiro, Suzuki Yuichi, Kuwahara Atsukazu, Yoshiki Hatsumi, Sada Kiyonao, Muramatsu Ikunobu, Anisuzzaman Abu Syed Md, Taniguchi Takanobu
Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan; Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan.
FEBS Lett. 2015 Nov 30;589(23):3640-7. doi: 10.1016/j.febslet.2015.10.029. Epub 2015 Oct 28.
Impaired intestinal barrier function is one of the critical issues in inflammatory bowel diseases. The aim of this study is to investigate muscarinic cholinoceptor (mAChR)-mediated signaling for the amelioration of cytokine-induced barrier dysfunction in intestinal epithelium. Rat colon challenged with TNF-α and interferon γ reduced transepithelial electrical resistance (TER). This barrier injury was attenuated by muscarinic stimulation. In HT-29/B6 intestinal epithelial cells, muscarinic stimulation suppressed TNF-α-induced activation of NF-κB signaling and barrier disruption. Finally, muscarinic stimulation promoted the shedding of TNFR1, which would be a mechanism for the attenuation of TNF-α/NF-κB signaling and barrier disruption via mAChR.
肠道屏障功能受损是炎症性肠病的关键问题之一。本研究旨在探讨毒蕈碱型胆碱能受体（mAChR）介导的信号传导对细胞因子诱导的肠上皮屏障功能障碍的改善作用。用肿瘤坏死因子-α（TNF-α）和干扰素γ刺激大鼠结肠可降低跨上皮电阻（TER）。毒蕈碱刺激可减轻这种屏障损伤。在HT-29/B6肠上皮细胞中，毒蕈碱刺激可抑制TNF-α诱导的核因子κB（NF-κB）信号通路激活和屏障破坏。最后，毒蕈碱刺激促进肿瘤坏死因子受体1（TNFR1）的脱落，这可能是通过mAChR减轻TNF-α/NF-κB信号通路和屏障破坏的一种机制。
