Role of TLR5 in inflammation and tissue damage after intestinal ischemia-reperfusion injury

被引：16

作者：

Ito, Homare ^{[1
,2
]}

Sadatomo, Ai ^{[1
,2
]}

Inoue, Yoshiyuki ^{[1
,2
]}

Yamada, Naoya ^{[1
]}

Aizawa, Emi ^{[1
]}

Hishida, Erika ^{[1
]}

Kamata, Ryo ^{[1
]}

Karasawa, Tadayoshi ^{[1
]}

Kimura, Hiroaki ^{[1
]}

Watanabe, Sachiko ^{[1
]}

Komada, Takanori ^{[1
]}

Horie, Hisanaga ^{[2
]}

Kitayama, Joji ^{[2
]}

Sata, Naohiro ^{[2
]}

Takahashi, Masafumi ^{[1
]}

机构：

[1] Jichi Med Univ, Ctr Mol Med Gen & Transplant Surg, Div Inflammat Res, Shimotsuke, Tochigi, Japan

[2] Jichi Med Univ, Dept Surg, Div Gastroenterol Gen & Transplant Surg, Shimotsuke, Tochigi, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2019年 / 519卷 / 01期

基金：

日本学术振兴会;

关键词：

Cytokines; Inflammation; Interleukin; Intestine; Lung; CONTRIBUTES;

D O I：

10.1016/j.bbrc.2019.08.083

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2019 Elsevier Inc. All rights reserved.

引用

页码：15 / 22

页数：8

共 24 条

[1] TLR5, a Novel and Unidentified Inflammatory Mediator in Rheumatoid Arthritis that Correlates with Disease Activity Score and Joint TNF-α Levels
Chamberlain, Nathan D.
Vila, Olga M.
Volin, Michael V.
Volkov, Suncica
Pope, Richard M.
Swedler, William
Mandelin, Arthur M., II
Shahrara, Shiva
[J]. JOURNAL OF IMMUNOLOGY, 2012, 189 (01) : 475 - 483
[2] Intestinal Epithelial Cell Toll-like Receptor 5 Regulates the Intestinal Microbiota to Prevent Low-Grade Inflammation and Metabolic Syndrome in Mice
Chassaing, Benoit
Ley, Ruth E.
Gewirtz, Andrew T.
[J]. GASTROENTEROLOGY, 2014, 147 (06) : 1363 - +
[3] The two faces of IKK and NF-κB inhibition:: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion
Chen, LW
Egan, L
Li, ZW
Greten, FR
Kagnoff, MF
Karin, M
[J]. NATURE MEDICINE, 2003, 9 (05) : 575 - 581
[4] HMGB1 Activates Proinflammatory Signaling via TLR5 Leading to Allodynia
Das, Nabanita
Dewan, Varun
Grace, Peter M.
Gunn, Robin J.
Tamura, Ryo
Tzarum, Netanel
Watkins, Linda R.
Wilson, Ian A.
Yin, Hang
[J]. CELL REPORTS, 2016, 17 (04): : 1128 - 1140
[5] Leukocyte TLR5 deficiency inhibits atherosclerosis by reduced macrophage recruitment and defective T-cell responsiveness
Ellenbroek, Guilielmus H. J. M.
van Puijvelde, Gijs H. M.
Anas, Adam A.
Bot, Martine
Asbach, Miriam
Schoneveld, Arjan
van Santbrink, Peter J.
Foks, Amanda C.
Timmers, Leo
Doevendans, Pieter A.
Pasterkamp, Gerard
Hoefer, Imo E.
van der Poll, Tom
Kuiper, Johan
de Jager, Saskia C. A.
[J]. SCIENTIFIC REPORTS, 2017, 7
[6] Ischemia and reperfusion-from mechanism to translation
Eltzschig, Holger K.
Eckle, Tobias
[J]. NATURE MEDICINE, 2011, 17 (11) : 1391 - 1401
[7] Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome
Englert, Joshua A.
Bobba, Christopher
Baron, Rebecca M.
[J]. JCI INSIGHT, 2019, 4 (02)
[8] Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition
Fulde, Marcus
Sommer, Felix
Chassaing, Benoit
van Vorst, Kira
Dupont, Aline
Hensel, Michael
Basic, Marijana
Klopfleisch, Robert
Rosenstiel, Philip
Bleich, Andre
Baeckhed, Fredrik
Gewirtz, Andrew T.
Hornef, Mathias W.
[J]. NATURE, 2018, 560 (7719) : 489 - +
[9] Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research
Gonzalez, Liara M.
Moeser, Adam J.
Blikslager, Anthony T.
[J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2015, 308 (02): : G63 - G75
[10] Murine Model of Intestinal Ischemia-reperfusion Injury
Gubernatorova, Ekaterina O.
Perez-Chanona, Ernesto
Koroleva, Ekaterina P.
Jobin, Christian
Tumanov, Alexei V.
[J]. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2016, (111):

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