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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Suppression of TLR Signaling by Targeting TIR domain-Containing Proteins
Current Protein & Peptide Science Strain and Strain Rate Imaging by Echocardiography - Basic Concepts and Clinical Applicability
Current Cardiology Reviews Detection and Transport Mechanisms of Circulating microRNAs in Neurological, Cardiac and Kidney Diseases
Current Medicinal Chemistry Anabolic Androgenic Steroid (AAS) Related Deaths: Autoptic, Histopathological and Toxicological Findings
Current Neuropharmacology Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke
Current Neurovascular Research Oxidative Stress in the ICU
Current Nutrition & Food Science Pharmacologic Modulators of Soluble Guanylate Cyclase/Cyclic Guanosine Monophosphate in the Vascular System - From Bench Top to Bedside
Current Vascular Pharmacology Anesthetic Neuroprotection: Antecedents and An Appraisal of Preclinical and Clinical Data Quality
Current Pharmaceutical Design Energy Provisioning and Inflammasome Activation: The Pivotal Role of AMPK in Sterile Inflammation and Associated Metabolic Disorders
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Overview of Systems Biology and Omics Technologies
Current Medicinal Chemistry Therapeutic Potential of Neuregulin in Cardiovascular System: Can we Ignore the Effects of Neuregulin on Electrophysiology?
Mini-Reviews in Medicinal Chemistry Preeclampsia: Placental Origins, New Predictors and New Therapeutic Strategies
Current Women`s Health Reviews Multimodality Imaging in Acute Ischemic Stroke
Current Medical Imaging Mitochondrial Aldehyde Dehydrogenase, A Potential Drug Target for Protection of Heart and Brain from Ischemia/Reperfusion Injury
Current Drug Targets Role of Cannabinoids and Endocannabinoids in Cerebral Ischemia
Current Pharmaceutical Design Natural Antioxidants: Therapeutic Prospects for Cancer and Neurological Diseases
Mini-Reviews in Medicinal Chemistry Facing Up the ROS Labyrinth - Where To Go?
Current Vascular Pharmacology n-3 Polyunsaturated Fatty Acids as Signal Transduction Modulators and Therapeutical Agents in Cancer
Current Signal Transduction Therapy Pharmacological Benefits of Active Components of Natural Products Against Traumatic Brain Injury - A Review
Current Pharmacogenomics and Personalized Medicine Therapeutic Effects of Progesterone in Animal Models of Neurological Disorders
CNS & Neurological Disorders - Drug Targets