In silico identification of components of the Toll-like receptor (TLR) signaling pathway in clustered chicken expressed sequence tags (ESTs)

28 Background: The discovery of the link between H. pylori and gastric cancer may be the most direct proof that bacterial signaling and host response can result in carcinogenesis. Accumulating evidence supports that activation of the Toll-like receptor (TLR) signaling pathway by microbes is associated with the development of GI malignancies. Using the modified Levrat model of gastroduodenojejunal reflux which mimics the physiological and molecular sequence of human EAC in the rat, this study profiles the expression of genes central to TLR-mediated signal transduction as well as characterizes the esophageal microbiome across the spectrum of EAC development. Methods: Modified Levrat’s surgery induced chronic acid reflux in Sprague-Dawley’s with harvest of esophagus 40 weeks post-surgery. Macordissection of normal adjacent epithelium, Barrett’s esophagus (BE), dysplasia and EAC tumor was performed followed by RNA/DNA isolation. Five samples per group were selected for gene expression profiling on the Qiagen TLR Signaling Pathway PCR Array as well as microbiome analysis by IBIS technology. Validation of IBIS was performed by fluorescence in situ hybridization (FISH). Results: Gene expression analysis identified TLRs 1-3 and 6, 7, 9 as significantly upregulated in EAC compared to normal esophagus. TLR 1 and 5 were significantly upregulated in dysplasia. TLR 1 was significantly upregulated in BE and normal adjacent epithelium. Thirty seven genes involved in the TLR signaling pathway were dysregulated in EAC, 30 in dysplasia, 21 in BE and 23 in normal adjacent. IBIS analysis revealed a prevalence of E. coli in BE and EAC which was validated by FISH. Conclusions: Toll-like receptor (TLR) signaling pathway responses to E. coli may participate in the development of EAC. E. coli may be a potential risk factor for EAC requiring further clinical validation.

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Hepatitis C Virus Nonstructural Protein 5A Modulates the Toll-Like Receptor-MyD88-Dependent Signaling Pathway in Macrophage Cell Lines

Journal of Virology ◽

10.1128/jvi.00649-07 ◽

2007 ◽

Vol 81 (17) ◽

pp. 8953-8966 ◽

Cited By ~ 115

Author(s):

Takayuki Abe ◽

Yuuki Kaname ◽

Itsuki Hamamoto ◽

Yoshimi Tsuda ◽

Xiaoyu Wen ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Signaling Pathway ◽

Cell Lines ◽

Immune Cells ◽

Cytokine Production ◽

Toll Like Receptor ◽

Macrophage Cell ◽

Tlr Signaling ◽

Tlr Signaling Pathway

ABSTRACT Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries; however, the mechanism through which HCV evades the immune surveillance system remains obscure. Blood dendritic cells (DCs) play a pivotal role in the recognition of viral infection and the induction of innate and adaptive immune responses. Several reports suggest that HCV infection induces the dysfunction of DCs in patients with chronic hepatitis C. Toll-like receptor (TLR) has been shown to play various roles in many viral infections; however, the involvement of HCV proteins in the TLR signaling pathway has not yet been precisely elucidated. In this study, we established mouse macrophage cell lines stably expressing HCV proteins and determined the effect of HCV proteins on the TLR signaling pathways. Immune cells expressing NS3, NS3/4A, NS4B, or NS5A were found to inhibit the activation of the TLR2, TLR4, TLR7, and TLR9 signaling pathways. Various genotypes of NS5A bound to MyD88, a major adaptor molecule in TLR, inhibited the recruitment of interleukin-1 receptor-associated kinase 1 to MyD88, and impaired cytokine production in response to TLR ligands. Amino acid residues 240 to 280, previously identified as the interferon sensitivity-determining region (ISDR) in NS5A, interacted with the death domain of MyD88, and the expression of a mutant NS5A lacking the ISDR partially restored cytokine production. These results suggest that the expression of HCV proteins modulates the TLR signaling pathway in immune cells.

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Luteolin Targets the Toll-Like Receptor Signaling Pathway in Prevention of Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice

Nutrients ◽

10.3390/nu10101415 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1415 ◽

Cited By ~ 11

Author(s):

Eun-Young Kwon ◽

Myung-Sook Choi

Keyword(s):

Insulin Resistance ◽

Signaling Pathway ◽

Low Grade ◽

Toll Like Receptor ◽

High Fat ◽

Gene Expressions ◽

Tlr Signaling ◽

Low Grade Inflammation ◽

Tlr Signaling Pathway

This study was to investigate the protective role of luteolin on inflammation-mediated metabolic diseases, focusing on the role of luteolin in the modulation of the Toll-like receptor (TLR) signaling pathway. C57BL/6J mice were fed a normal, high-fat, or high-fat + 0.005% (w/w) luteolin diet for 16 weeks. Luteolin improved chronic low-grade inflammation by modulating the TLR signaling pathway, resulting in reduced pro-inflammatory cytokines and macrophage accumulation. A positive relationship was detected between gene expressions of Tlr5, Map2k7, Mapk12, Mapk13, and Mapk9 and lipogenesis in epididymal white adipose tissue (eWAT) of luteolin-treated mice, which was linked to attenuation of hepatic lipotoxicity by increasing free fatty acid (FFA) flux to the WAT. Luteolin prevented fibrosis by decreasing extracellular matrix accumulation and cathepsin gene expressions, while enhancing the hepatic antioxidant system. Emr1 and Ccl7, important markers inducing low-grade inflammation, were affected by advanced age and greater body weight, which were normalized by luteolin treatment. Luteolin improved insulin resistance by normalizing pancreatic islet dysfunction and differentially modulating the plasma glucagon-like peptide-1 and gastric inhibitory polypeptide levels. Our results suggest that luteolin ameliorates diet-induced obesity and its comorbidities. Overall, this study provides novel insights into the effect of luteolin on the links among adiposopathy, insulin resistance, hepatic steatosis, and fibrosis.

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