No abstract available.
Toll-Like Receptors*

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in a wide spectrum of cell types that recognize distinctive ligands and subsequently activate adaptive immune responses. TLR ligands are considered a promising target for development of immunomodulatory agents. Extensive clinical investigations are currently underway to develop TLR ligands-based non-specific immunostimulants and vaccine adjuvants. It has been well accepted that cancer cells develop a strategy to avoid host immune responses by producing inhibitory molecules. In addition, tumor-associated antigens are often not strong enough to induce effective anti-cancer immune responses. In this context, immunostimulants or adjuvants are critically required for more effective cancer immunotherapies. Here, we discuss recent progresses in the field of cancer immunotherapy under special emphasis on the TLR ligands as a component of immunostimulatory agents.
Adjuvants, Immunologic ; Immunotherapy ; Ligands ; Receptors, Pattern Recognition ; Toll-Like Receptors

Toll-like receptor 9 binds to DNA from bacteria or viruses and activates a signaling pathway that leads to the induction of proinflammatory cytokines and type I interferon. Adaptor complex AP-3 was required for TLR9 trafficking and the production of type I interferon but not for proinflammatory cytokines. This suggests that TLR9 signaling is regulated by the subcellular localization of the receptor.
Bacteria ; Cytokines ; DNA ; Interferon Type I ; Toll-Like Receptor 9 ; Toll-Like Receptors

In the last few years, a spectrum of dendritic cells(DCs), including toll like receptors(TLRs), might play a critical role in regulating allergy and asthma. DC plays a central role in initiating immune responses, linking innate and adaptive responses to pathogen. Human peripheral blood has three non- overlapping dendritic subset that expressed various 11 TLRs. These dendritic subsets and TLR contribute significant polarizing influences on T helper differentiation, but how this comes about is less clear. A better understanding of DC immunobiology may lead to the comprehension of allergy pathophysiology to prevent early stage allergic march.
Asthma ; Comprehension ; Dendritic Cells* ; Humans ; Hypersensitivity ; Toll-Like Receptors

Translocator protein 18 kDa (TSPO) is a mitochondrial protein highly expressed on reactive microglia and astrocytes, and is considered as a biomarker for neurodegeneration and brain damage, especially neuroinflammation. Toll-like receptors (TLRs) are closely related with inflammatory responses of microglia and astrocytes and these signaling pathways regulate neuroinflammation. Previous reports have identified the anti-inflammatory effects of TSPO ligands, however study of their effects in relation to the TLR signaling was limited. Here, we investigated the effects of five representative TSPO ligands on microglia and astrocytes following activation by various TLR ligands. Our results show that TSPO ligands reduce the pro-inflammatory response elicited by the TLR ligands with more profound effects on microglia than astrocytes.
Astrocytes* ; Brain ; Ligands* ; Microglia* ; Mitochondrial Proteins ; Toll-Like Receptors

Objective: To investigate the expression of toll-like receptor (TLR)-2, 4 and 9 in idiopathic inflammatory myopathies (IIMs). Methods: The expression of TLR-2, 4 and 9 was measured by real-time RT-PCR and immunohistochemical stain (IHS) from muscle tissues in patients with IIMs and controls. Results: The expression levels of TLR-2, 4 and 9 in IIMs were significantly higher than controls. TLR-2, 4 and 9 were mainly expressed on sarcolemma of muscle fibers, perimysial vascular endothelium and infiltrating inflammatory cells in dermatomyositis, whereas, they were mainly expressed on sarcolemma of muscle fibers, destructed muscle fibers, and enodmysial infiltrating inflammatory cells in polymyositis. Conclusion: TLR-2, 4 and 9 were highly expressed in muscle tissue of IIMs. These results suggest that TLR-2, 4 and 9 play a role in pathogenesis of IIMs.
Dermatomyositis ; Endothelium, Vascular ; Humans ; Myositis* ; Polymyositis ; Sarcolemma ; Toll-Like Receptors*

Keloid is a kind of pathological scar of skin, which would seriously impair patient's quality of life. But until today, no reliable theory to explain the development of keloid has been established. Recent studies have found that toll-like receptors plays an important role in the formation of keloid. This article reviews the advances in the research of toll-like receptors making contribution to the pathogenesis of keloid. Further researches could lead to a new strategy in treating keloid.
Animals ; Humans ; Keloid ; pathology ; Toll-Like Receptors ; Wound Healing

Humans ; Otitis Media ; etiology ; pathology ; Toll-Like Receptors

Butyrate, normally produced by probiotics in the gut, not only provides energy for cells, but also changes the phosphorylation, acetylation and methylation levels of many proteins in cells. As a result, it affects the expression of many genes and the transmission of cell signals. Through G protein-coupled receptors, butyrate promotes the secretion of intestinal mucus and the formation of epithelial barriers, and attenuates the impacts of the pathogenic bacteria and their metabolites on human body. The Toll-like receptors (TLRs) are a group of pattern recognition receptors, and their activation causes the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus and eventually leads to expression and secretion of various pro-inflammatory factors and chemokines. The expression of TLRs is also involved in the pathogenesis of some inflammatory diseases and tumors. The purpose of this review is to summarize the effects of butyrate on TLRs and their downstream signaling pathways. We not only summarized the production of butyrate, the expression of TLRs and the influence of their interaction on the body under the conditions of inflammation and tumor, but also discussed the potential role of butyrate as a bacterial metabolite in the treatments of some human diseases.
Humans ; Butyrates ; Toll-Like Receptors ; Acetylation ; Phosphorylation ; Inflammation

We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the IL-1alpha gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of IL-1alpha . Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and IL-1alpha. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and IL-1alpha induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of IL-1alpha . These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of IL-1alpha in monocytic cells via multiple signaling pathways.
Cholesterol ; Cytokines ; Inflammation ; Interleukin-1 ; Interleukin-1alpha* ; Toll-Like Receptors*