Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways

• 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.
• Potential therapeutic targets involved in provoking the inflammation include Toll-like receptors (TLRs) and their downstream signaling molecules responsible for their critical role in various chronic inflammatory diseases.
• Signaling pathways via TLR4 activate various transcription factors like NF-κB, AP1, STAT1, and IRFs. Inhibition of these targets and their upstream signaling molecules provide a potential therapeutic approach to treat inflammatory diseases.
• In this article, we have highlighted the already known inflammatory signaling players and discussed about the recent advancements in discovery of potential targets within the major TLR-4 mediated pathway.
• SiR4 activs like nuclear factor kappa-light-chain-enhancer (NF-κB), activator protein 1 (AP1), signal transducers and activators of tran(STAT1) and nterferon regulatory factors (IRF's),

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.