Abstract
Toll-like receptors (TLRs) are sensors of microbial products that initiate host defense responses in multicellular organisms. They are mainly linked to innate immunity and bridging to adaptive immunity, signaling through different TLRs responsible for a wide range of biological responses. The intracellular signaling pathways through Toll/interleukin- 1 receptor (IL-1R) domains result in recruitment of the cytoplasmic adaptor molecules, with subsequent activation of a signaling cascade leading to nuclear factor-κ B (NF-κB). TLR-signaling induces host inflammatory response and the inflammation becomes more severe in the absence of several extra and intra cellular negative regulators of TLR-signaling. In the intestine, TLR-dependent activation of NF-κB plays a vital role in maintaining epithelial homeostasis as well as regulating infections and inflammation, while dysregulation of TLR-signaling is associated with the pathogenesis of inflammatory bowel diseases (IBD). Recent findings regarding innate immunity-mediated regulation of intestinal pathophysiology prove that development of new drugs targeting TLRs including antagonists of TLR-signaling and agonists of their negative regulators has a potential impact on therapeutic strategies for intestinal inflammatory diseases.
Keywords: CRX-526, TLR expression, pro-inflammatory, Endotoxin, inflammatory bowel diseases (IBD)
Current Pharmaceutical Design
Title: Therapeutic Targeting of Toll-Like Receptors in Gastrointestinal Inflammation
Volume: 12 Issue: 32
Author(s): Shunji Ishihara, Mohammad A.K. Rumi, Cesar-F. Ortega-Cava, Hideaki Kazumori, Yasunori Kadowaki, Norihisa Ishimura and Yoshikazu Kinoshita
Affiliation:
Keywords: CRX-526, TLR expression, pro-inflammatory, Endotoxin, inflammatory bowel diseases (IBD)
Abstract: Toll-like receptors (TLRs) are sensors of microbial products that initiate host defense responses in multicellular organisms. They are mainly linked to innate immunity and bridging to adaptive immunity, signaling through different TLRs responsible for a wide range of biological responses. The intracellular signaling pathways through Toll/interleukin- 1 receptor (IL-1R) domains result in recruitment of the cytoplasmic adaptor molecules, with subsequent activation of a signaling cascade leading to nuclear factor-κ B (NF-κB). TLR-signaling induces host inflammatory response and the inflammation becomes more severe in the absence of several extra and intra cellular negative regulators of TLR-signaling. In the intestine, TLR-dependent activation of NF-κB plays a vital role in maintaining epithelial homeostasis as well as regulating infections and inflammation, while dysregulation of TLR-signaling is associated with the pathogenesis of inflammatory bowel diseases (IBD). Recent findings regarding innate immunity-mediated regulation of intestinal pathophysiology prove that development of new drugs targeting TLRs including antagonists of TLR-signaling and agonists of their negative regulators has a potential impact on therapeutic strategies for intestinal inflammatory diseases.
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Cite this article as:
Ishihara Shunji, Rumi A.K. Mohammad, Ortega-Cava Cesar-F., Kazumori Hideaki, Kadowaki Yasunori, Ishimura Norihisa and Kinoshita Yoshikazu, Therapeutic Targeting of Toll-Like Receptors in Gastrointestinal Inflammation, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743448
DOI https://dx.doi.org/10.2174/138161206778743448 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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