title: Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways.
abstract: Inflammation is set off when innate immune cells detect infection or tissue injury. Tight control of the severity, duration, and location of inflammation is an absolute requirement for an appropriate balance between clearance of injured tissue and pathogens versus damage to host cells. Impeding the risk associated with the imbalance in the inflammatory response requires precise identification of potential therapeutic targets involved in provoking the inflammation. Toll-like receptors (TLRs) primarily known for the pathogen recognition and subsequent immune responses are being investigated for their pathogenic role in various chronic diseases. A mammalian homologue of Drosophila Toll receptor 4 (TLR4) was shown to induce the expression of genes involved in inflammatory responses. Signaling pathways via TLR4 activate various transcription factors like Nuclear factor kappa-light-chain-enhancer (NF-κB), activator protein 1 (AP1), Signal Transducers and Activators of Transcription family of transcription factors (STAT1) and Interferon regulatory factors (IRF's), which are the key players regulating the inflammatory response. Inhibition of these targets and their upstream signaling molecules provides a potential therapeutic approach to treat inflammatory diseases. Here we review the therapeutic targets involved in TLR-4 signaling pathways that are critical for suppressing chronic inflammatory disorders.
authors: Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology (IIT), Indore, MP, India.
authors: Anjali
authors: A
authors: Roy
authors: Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology (IIT), Indore, MP, India.
authors: Mansi
authors: M
authors: Srivastava
authors: Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore (IITI), Indore, MP, India.
authors: Uzma
authors: U
authors: Saqib
authors: Center for Inflammation & Epigenetics, Houston Methodist Research Institute, Houston, TX, USA.
authors: Dongfang
authors: D
authors: Liu
authors: National Institute of Animal Biotechnology (NIAB), Hyderabad, Telangana, India.
authors: Syed M
authors: SM
authors: Faisal
authors: Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology (IIT), Indore, MP, India.
authors: Subi
authors: S
authors: Sugathan
authors: Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology (IIT), Indore, MP, India.
authors: Suman
authors: S
authors: Bishnoi
authors: Center for Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology (IIT), Indore, MP, India. Electronic address: msb@iiti.ac.in.
authors: Mirza S
authors: MS
authors: Baig
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1
keywords: AP1; IRF's; Inflammation; NF-κB; STAT1; TLR4 signaling