Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: Pathogenesis and therapeutic implications

Chan, Kelvin; Wong, Kwong F.; Luk, John M.

doi:10.3748/wjg.15.4745

Cited by 55 publications

(46 citation statements)

References 25 publications

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“…It has been reported that TLR-4 expression is increased in the intestinal mucosa of mice, rats, and humans with NEC and that this TLR-4 expression in enterocytes may lead to an increase in death of the cells that line the intestine through the process of apoptosis [24][25][26]. These findings show that TLR-4 expression may lead to the development of intense and harmful effects in promoting intestinal injury and decreasing the ability of mucosal repair in the newborn small intestine.…”

Section: Discussionmentioning

confidence: 72%

Experimental immunology The response of Toll-like receptors to glutamine in neonatal rat intestine

Karaoğlu¹,

Tunç²,

Aydemir³

et al. 2012

cejoi

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Background: There are several barrier systems in the newborn gastrointestinal tract and one of the most important among these are the Toll-like receptors (TLRs). The aim of this study was to examine the effect of glutamine on Toll-like receptors 2 (TLR-2), TLR-4, and TLR-9 levels in the newborn gut.Material and methods: Rats were randomly assigned to three experimental groups. Group I (control at day 0) (n = 9), group II (control at day 10) (n = 9): oral distilled water, group III (study group) (n = 9): oral glutamine (200 mg/kg/day).

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Section: Discussionmentioning

confidence: 72%

Experimental immunology The response of Toll-like receptors to glutamine in neonatal rat intestine

Karaoğlu¹,

Tunç²,

Aydemir³

et al. 2012

cejoi

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“…He et al (19) observed that LPS could significantly inhibit apoptosis of gastric cancer cells and that this effect was considered to be closely associated with the activation of TLR4 and its downstream gene, nuclear factor-κB (NF-κB). Although CD14 is a high-affinity receptor of LPS, the CD14 protein has neither a transmembrane domain nor a cytoplasmic segment, and therefore, its effect on signal transmission into the nucleus is performed in coordination with TLR4 (20). Baumann et al (21) reported that the level of CD14 protein may affect TLR activity and thus interfere with the effect of certain anti-cancer therapies or anti-viral reactions.…”

Section: Discussionmentioning

confidence: 99%

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

Zhang

Nie

et al. 2015

Molecular Medicine Reports

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Abstract. The present study examined the role of CD14 in the regulation of lipopolysaccharide (LPS)-induced effects on gastric cancer cells. MGC-803 cells were stably transfected with CD14 short hairpin (sh)RNA and treated with LPS, followed by assessment of cell proliferation, apoptosis and gene expression using a cell counting kit-8 assay, flow cytometry, reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cells subjected to CD14 knockdown were treated with 10 g/ml LPS and injected into nude mice to form tumor xenografts. CD14 shRNA-transfected MGC-803 cells did not exhibit any significant changes in cell viability compared with the control cells (P>0.05), but cell viability was markedly increased in the wild-type (WT) + LPS group (P<0.05). In contrast to the WT + LPS group, the cell viability of the sh-CD14 + LPS group was markedly decreased (P<0.05). In addition, compared with those in the controls, the level of sh-CD14 cell apoptosis did not change significantly; however, it was markedly reduced in the LPS group. Compared with that in the WT + LPS group, the rate of apoptosis in the sh-CD14 + LPS group increased to a certain extent, while it remained lower in the control group. In addition, compared with that in the control, the expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6 and IL-12, and human β-defensin 2 was significantly increased in the WT + LPS group, while, compared with that in the WT + LPS group, the expression of these genes was markedly reduced in the sh-CD14 + LPS group (P<0.05). The nude mouse experiments further confirmed the in vitro data, including the finding that LPS promoted the growth of xenografts, but knockdown of CD14 expression reduced the response of tumor cells to LPS treatment. In conclusion, LPS induced cell viability and the release of inflammatory cytokines, but inhibited gastric cancer cell apoptosis. Knockdown of CD14 expression had no significant effect on gastric cancer malignancy, but mediated LPS signal transduction. IntroductionGastric cancer is one of the most common types of cancer globally and accounted for 989,600 ovel cases and 738,000 cancer-associated fatalities in 2008 (1). >70% of novel gastric cancer cases and fatalities occur in the developing countries, while they have declined in the majority of developed countries, including countries in North America and Europe in previous decades (1). The risk factors for gastric cancer include Helicobacter (H.) pylori infection, history of tobacco smoking, and consumption of smoked foods, salted meat or fish and pickled vegetables. However, intake of fresh fruits and vegetables appears to lower the risk of gastric cancer (1). Regional variations in gastric cancer prevalence reflect the differences in dietary patterns and the prevalence of H. pylori infection (2). H. pylori is an aerobic Gram-negative bacterium found in the stomach, which causes chronic gastritis, peptic ulcers and gastric cancer. Thus, H. pylori infection has been classified as a class I carcinog...

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“…When digested, E. coli contaminated food can cause watery diarrhea. Other more severe and rare diseases are kidney failure, blindness, paralysis, Necrotizing Entero Colitis (NEC) and even death [2].…”

Section: Introductionmentioning

confidence: 99%

“…If LPS gains entry to the bloodstream, it can bind the host cells, such as macrophages, through the CD14 receptors [3,4], triggering a cascade of adverse systemic responses and organ failure (septic shock) [5,6]. In the United States, there are an estimated 751,000 cases of severe sepsis every year [2].…”

Section: Introductionmentioning

confidence: 99%

“…Here, cells and tissue are destroyed by the LPS and inflammation does occur. Lastly, LPS is also a causal factor of NEC (necrotizing enterocolitis), a disorder found mostly in newborn infants [2]. If LPS gains entry to the bloodstream, it can bind the host cells, such as macrophages, through the CD14 receptors [3,4], triggering a cascade of adverse systemic responses and organ failure (septic shock) [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Anti-LPS Test Strip for the Detection of Food Contaminated with Salmonella and E. coli

Wang¹,

Molina²,

Prima³

et al. 2011

JMBT

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Enterobacteria such as E. coli and Salmonella release an endotoxin, or lipopolysaccharide (LPS) that contributes to food poisoning symptoms. We hypothesize that LPS could be detected by a simple strip test, thus detecting the presence of enterobacteria in food. Here we described the development of a novel Anti-LPS detection strip test. Flexible polystyrene test strips with an absorbent poly (vinylidene fluoride) membrane adhered onto one end were exposed to various dilutions of food or bacterial sources. This was followed by the sequential incubation with a primary anti-LPS antibody, biotinylated secondary antibody, and streptavidin-linked enzyme alkaline phosphatase. The test strip was then developed with substrate 5-bromo-4-chloro-3-indolyl phosphate/nitroblue tetrazolium. Thus, the presence of purple precipitate product would indicate the presence of LPS and enterobacteria. The intensity or darkness of the color was quantified densitometrically and compared to LPS standard curve. The test strip assay was shown to readily detect as low as 25 ng/mL of purified LPS. In addition, theanti-LPS test strip assay can sensitively detect and quantify LPS released by live E. coli into culture media. Finally, three food groups (strawberry slices, spinach leaves and ground beef) were inoculated with E. coli for two time points at room temperature and then rinse water from each food preparation was subjected to the anti-LPS test strip assay. For all three food groups, the test strip assay can readily detect and quantify both 8 h and 24 h bacteria contamination over their respective uncontaminated controls. In conclusion, a simple prototype anti-LPS strip test was developed to readily detect enterobacteria contamination of common food.

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Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: Pathogenesis and therapeutic implications

Cited by 55 publications

References 25 publications

Experimental immunology The response of Toll-like receptors to glutamine in neonatal rat intestine

Experimental immunology The response of Toll-like receptors to glutamine in neonatal rat intestine

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

Anti-LPS Test Strip for the Detection of Food Contaminated with Salmonella and E. coli

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