Homare Ito1, Ai Sadatomo1, Yoshiyuki Inoue1, Naoya Yamada2, Emi Aizawa2, Erika Hishida2, Ryo Kamata2, Tadayoshi Karasawa2, Hiroaki Kimura2, Sachiko Watanabe2, Takanori Komada2, Hisanaga Horie3, Joji Kitayama3, Naohiro Sata3, Masafumi Takahashi4. 1. Division of Inflammation Research, Center for Molecular Medicine, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan; Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan. 2. Division of Inflammation Research, Center for Molecular Medicine, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan. 3. Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan. 4. Division of Inflammation Research, Center for Molecular Medicine, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan. Electronic address: masafumi2@jichi.ac.jp.
Abstract
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.
Authors: Jingjuan Hu; Fan Deng; Bingcheng Zhao; Zebin Lin; Qishun Sun; Xiao Yang; Mei Wu; Shida Qiu; Yu Chen; Zhengzheng Yan; Sidan Luo; Jin Zhao; Weifeng Liu; Cai Li; Ke Xuan Liu Journal: Microbiome Date: 2022-03-03 Impact factor: 14.650