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Chylomicrons promote intestinal absorption of lipopolysaccharides
- Journal of Lipid Research,vol.50,no.1
, 2009
"... Abstract Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. The mechanism of fat-induced LPS absorption is unclear, however. Intestinal-epithelial cells can internalize LP ..."
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Abstract Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. The mechanism of fat-induced LPS absorption is unclear, however. Intestinal-epithelial cells can internalize LPS from the apical surface and transport LPS to the Golgi. The Golgi complex also contains newly formed chylomicrons, the lipoproteins that transport dietary longchain fat through mesenteric lymph and blood. Because LPS has affinity for chylomicrons, we hypothesized that chylomicron formation promotes LPS absorption. In agreement with our hypothesis, we found that CaCo-2 cells released more cell-associated LPS after incubation with oleic-acid (OA), a long-chain fatty acid that induces chylomicron formation, than with butyric acid (BA), a short-chain fatty acid that does not induce chylomicron formation. Moreover, the effect of OA was blocked by the inhibitor of chylomicron formation, Pluronic L-81. We also observed that intragastric triolein (TO) gavage was followed by increased plasma LPS, whereas gavage with tributyrin (TB), or TO plus Pluronic L-81, was not. Most intestinally absorbed LPS was present on chylomicron remnants (CM-R) in the blood. Chylomicron formation also promoted transport of LPS through mesenteric lymph nodes (MLN) and the production of TNFa mRNA in the MLN. Together, our data suggest that intestinal epithelial cells may release LPS on chylomicrons from cell-associated pools. Chylomicron-associated LPS may contribute to postprandial inflammatory responses or chronic diet-induced inflammation in chylomicron target tissues.—
CD14- and Toll-like receptor-dependent activation of bladder epithelial cells by lipopolysaccharide and type 1 piliated Escherichia coli. Infect. Immun
, 2003
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The role of epithelial toll-like receptor signaling in the pathogenesis of intestinal inflammation
- J. Leukoc. Biol
, 2008
"... Abstract: Emerging evidence suggests that the in-nate immune system, comprised of Toll-like recep-tors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflam-mation and in the response to invading pathogens. Although TLRs are thought to have predominantly ..."
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Abstract: Emerging evidence suggests that the in-nate immune system, comprised of Toll-like recep-tors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflam-mation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen recognition and bac-terial clearance by leukocytes, their dysregulation and unique signaling effects within intestinal epi-thelia in the setting of inflammation may have dev-astating consequences. For instance, activation of TLR4 in enterocytes leads to an inhibition of en-terocyte migration and proliferation as well as the induction of enterocyte apoptosis—factors that would be expected to promote intestinal injury while inhibiting intestinal repair. TLR signaling has been shown to be abnormal in several intestinal inflammatory diseases, including Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis. This review serves to examine the evidence regard-ing the patterns of expression and signaling of TLRs in the intestinal mucosa at basal levels and during physiologic stressors to gain insights into the pathogenesis of intestinal inflammation. We con-clude that the data reviewed suggest that epithelial TLR signaling—acting in concert with TLR signal-ing by leukocytes—participates in the development of intestinal inflammation. We further conclude that the evidence reviewed provides a rationale for the development of novel, epithelial-specific, TLR-based agents in the management of diseases of intestinal inflammation. J. Leukoc. Biol. 83:
Identification by microarray of a common pattern of gene expression in intact intestine and cultured intestinal cells . . .
, 2006
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Expression and Role of Anaphylatoxin Receptors on Human
, 2012
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The Role of CD14 and CTLA4 Gene Polymorphisms in Risk of Celiac Disease among Patients of Iranian Ethnicity Citation
"... Abstract Objective: Celiac disease (CD) is developed via autoimmune reactions against gluten which is mainly found in grains. Although HLA DQB1 locus is the most important genetic susceptibility to CD, some other variants such as A49G and G1359T of CTLA4 and CD14 genes respectively have been propos ..."
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Abstract Objective: Celiac disease (CD) is developed via autoimmune reactions against gluten which is mainly found in grains. Although HLA DQB1 locus is the most important genetic susceptibility to CD, some other variants such as A49G and G1359T of CTLA4 and CD14 genes respectively have been proposed as CD predisposing genetic factors in many various studies. We aimed to assess possible roles of A49G and G1359T polymorphisms in CD susceptibility in the Iranian population. Materials and Methods: In this case-control, one hundred CD patients and 100 healthy matched controls with average age of 30-33 years were selected. They were genotyped for both A49G and G1359T polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There was no association between genotypes of A49G variant of CTLA4 and risk of CD (p<0.05). The G1359T polymorphism of CD14 gene also did not show any significant association with risk of CD among the studied population. However, patients with CD14 T/T genotype were more classified in the severe form (Marsh III) of CD, showing border line significance (p<0.05). Conclusion: No association was identified between the combination of 1359T and A49G alleles with risk of CD. These lacks of association could be due to small sample size and considering further studies in various populations and ethnicities seems to be required.
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, 2013
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