𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine

✍ Scribed by Amlan Biswas; Jeanette Wilmanski; Huamei Forsman; Tomas Hrncir; Liming Hao; Helena Tlaskalova-Hogenova; Koichi S. Kobayashi

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
668 KB
Volume
41
Category
Article
ISSN
0014-2980

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria‐dependent colitis model in IL‐10‐deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL‐10^−/−^MyD88^−/−^ mice, IL‐10^−/−^TLR4^−/−^ mice exhibited reduced colitis compared to IL‐10^−/−^ mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK‐M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK‐M expression was reduced in mice re‐derived into a germ‐free environment, and introduction of commensal bacteria into germ‐free mice induced IRAK‐M expression. IL‐10^−/−^IRAK‐M^−/−^ mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis.

📜 SIMILAR VOLUMES

The role of MAPK in Kupffer cell toll-li
The role of MAPK in Kupffer cell toll-like receptor (TLR) 2-, TLR4-, and TLR9-mediated signaling following trauma-hemorrhage
✍ Bjoern M. Thobe; Michael Frink; Frank Hildebrand; Martin G. Schwacha; William J. 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 209 KB

## Abstract Severe injury deranges immune function and increases the risk of sepsis and multiple organ failure. Kupffer cells play a major role in mediating posttraumatic immune responses, in part via different Toll‐like receptors (TLR). Although mitogen‐activated protein kinases (MAPK) are key ele

An NF-χB-like element plays an essential
An NF-χB-like element plays an essential role in interleukin-1-mediated costimulation of the mouse interleukin-2 promoter
✍ Kirstin Strieker; Edgar Serfling; Peter H. Krammer; Werner Falk 📂 Article 📅 1993 🏛 John Wiley and Sons 🌐 English ⚖ 855 KB

Interleukin-1 (IL-1) costimulation is required for efficient IL-2 synthesis and IL-2 receptor (IG2R) expression of T cells. The molecular events leading to these effects are largely unknown. We utilized an IL-1-responsive and an IL-1non-responsive subclone of the mouse thymoma cell line EL4 to inves