Toll-like receptors and diseases

Iribarren, Pablo; Wang, Ji Ming

doi:10.1016/j.intimp.2011.08.010

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…15,18,19 The activationof TLRs can recruit specific adaptors, such as MyD88, TRIF, and TRAM, to initiate the downstream signaling transduction and thus lead to the generation of inflammatory mediators involved in the pathogenesis of autoimmune diseases. 19,20 Given the pivotal role of TLRs in inflammation and autoimmunity, the identification of therapeutic targets of innate immunity with TLRs agonists and antagonists has sparked great interest. In our previous study, we have found that LPS/TLR4-mediated inflammation played an important role in RA pathogenesis, while IL-29 (IFN-λ1) could enhance LPS/TLR4-mediated inflammatory response by activating NF-κB and its downstream signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…15,17 Accumulated evidence has strengthened the vital function of TLRs in the pathogenesis of autoimmune diseases, including RA, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome. 15,18,19 The activationof TLRs can recruit specific adaptors, such as MyD88, TRIF, and TRAM, to initiate the downstream signaling transduction and thus lead to the generation of inflammatory mediators involved in the pathogenesis of autoimmune diseases. 19,20 Given the pivotal role of TLRs in inflammation and autoimmunity, the identification of therapeutic targets of innate immunity with TLRs agonists and antagonists has sparked great interest.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of knowledge, TLRs are PRRs recognizing and defending exogenous pathogen‐associated molecular patterns or endogenous factors, which are called damage‐associated molecular patterns produced by cells apoptosis, strike or tissue damage . Accumulated evidence has strengthened the vital function of TLRs in the pathogenesis of autoimmune diseases, including RA, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome . The activationof TLRs can recruit specific adaptors, such as MyD88, TRIF, and TRAM, to initiate the downstream signaling transduction and thus lead to the generation of inflammatory mediators involved in the pathogenesis of autoimmune diseases .…”

Section: Discussionmentioning

confidence: 99%

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MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Wang

Zheng

Gao

et al. 2018

J of Cellular Biochemistry

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Currently published studies have implicated that microRNAs (miRNAs) including exosomes-encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes-encapsulated miR-548a-3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR-548a-3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR-548a-3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of miR-548a-3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down-regulated compared with healthy controls (n = 20). Serum exosomal miR-548a-3p was negatively associated with levels of CRP, RF, and ESR in serum of patients with RA. MiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells by regulating the TLR4/NF-κB signaling pathway. Accordingly, exosomes-delivered miR-548a-3p may be a critical factor predicting the disease activity of RA. MiR-548a-3p/TLR4/NF-κB axis can serve as promising targets for RA diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Wang

Zheng

Gao

et al. 2018

J of Cellular Biochemistry

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“…Toll-like receptors (TLRs) are a family of pattern-recognition receptors in the innate immune system. Exogenous and endogenous TLR ligands activate microglia that trigger inflammatory reactions in CNS ( 9 – 11 ). Recent studies using a mouse experimental brain abscess model have revealed a complex role for TLRs in the disease pathogenesis ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain

et al. 2018

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Acute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo, induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B+ CD45+ cells and colocalization of LC3B and lysosomal-associated membrane protein 1 in brain cells. Besides, we found that pharmacological inhibitors of PI3K, including the classical autophagy inhibitor 3-MA, reduced the recruitment of MC, microglial cell activation, and neurotoxicity induced by brain PGN injection. Collectively, our results suggest that PI3K pathways and autophagic response may participate in the PGN-induced microglial activation and MC recruitment to the brain. Thus, inhibition of these pathways could be therapeutically targeted to control acute brain inflammatory conditions.

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Environmentally Relevant Level of Aflatoxin B₁ Dysregulates Human Dendritic Cells Through Signaling on Key Toll-Like Receptors

et al. 2014

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Aflatoxins (AFs) are highly hazardous fungal biometabolites usually present in feeds and foods. Aflatoxin B (AFB) is the most toxic and a known carcinogen. Toll-like receptors (TLRs), highly expressed by myeloid dendritic cells (DC), are key innate immune-surveillance molecules. Toll-like receptors not only sense pathogen-associated molecular patterns but also contribute to infections and cancer. To assess AFB-TLR interactions on human myeloid DC, pure CD11c DC were generated from monocytes isolated from healthy individuals and then exposed to relevant level of AFB for 2 hours. Both quantitative polymerase chain reaction and flow cytometric assays were used to quantify, respectively, expression of TLR2 and TLR4 at the messenger RNA (mRNA) and protein levels in these DC. Levels of interleukin (IL) 1β, IL-6, and IL-10 were also analyzed in AFB- and mock-treated DC. Compared to nontreated CD11c DC, expression levels of both TLR2 and TLR4 mRNA and proteins were significantly upregulated in AFB-treated cells. Further, although IL-10 levels in AFB-treated DC were similar to those in the mock-treated DC, the AFB-exposed DC secreted higher amounts of IL-1β and IL-6. Dendritic cells are sensitive to environmentally relevant level of AFB, and TLR2 and TLR4 are involved in sensing AFB Considering the broad roles of TLR2, TLR4, and DC in immunity and infections, our novel findings open a new door to understanding the molecular mechanisms and functional consequences of AFB in inducing immunodysregulation, immunotoxicity, and thus (non)infectious diseases in humans.

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Toll-like receptors and diseases

Cited by 3 publications

References 9 publications

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain

Environmentally Relevant Level of Aflatoxin B₁ Dysregulates Human Dendritic Cells Through Signaling on Key Toll-Like Receptors

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Toll-like receptors and diseases

Cited by 3 publications

References 9 publications

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

MiR‐548a‐3p regulates inflammatory response via TLR4/NF‐κB signaling pathway in rheumatoid arthritis

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain

Environmentally Relevant Level of Aflatoxin B1 Dysregulates Human Dendritic Cells Through Signaling on Key Toll-Like Receptors

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Environmentally Relevant Level of Aflatoxin B₁ Dysregulates Human Dendritic Cells Through Signaling on Key Toll-Like Receptors