Serum lipopolysaccharide-binding protein and soluble CD14 are markers of disease activity in patients with Crohnʼs disease

Lakatos, László; Kiss, László; Palatka, Károly; Altorjay, István; Antal‐Szalmás, Péter; Palyu, Eszter; Udvardy, M.; Molnár, Tamás; Farkas, Klaudia; Veres, Gábor; Hársfalvi, Jolán; Papp, J.; Papp, Mária

doi:10.1002/ibd.21402

Cited by 72 publications

(60 citation statements)

References 39 publications

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“…Shed CL as well as the intestinal phospholipid barrier may represent another mechanism by which monophosphorylated family Bacteroidaceae-type LPS in the intestinal lumen due to significantly lower binding to LBP and transfer to CD14 (52) is neutralized before engagement of TLR4. In addition, both LBP and CD14 are made by intestinal epithelial cells (62,63), and evidence that they contribute to intestinal homeostasis has been reported (64,65). Furthermore, modulation of TLR4 activity by LPB may have some clinical utility in treating necrotizing enterocolitis (66).…”

Section: Discussionmentioning

confidence: 99%

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Coats

Hashim

Paramonov

et al. 2016

Appl Environ Microbiol

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Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCEThe guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders.T he intestinal tract is constantly exposed to the potentially harmful effects of lipopolysaccharide (LPS), commonly referred to as endotoxin. Both internal sources, such as the intestinal microbiome, and external sources, such as food, provide a constant potential for endotoxin-mediated local or systemic injury. Several different innate and adaptive protective mechanisms present in the intestine facilitate a homeostatic relationship with the resident commensal microbiota and buffer food intake such that LPS does not impair normal intestinal tissue functions (1-5).Studies have shown that a major mechanism by which the intestine limits exposure to the potentially harmful effects of LPS is by preventing intestinal LPS-epithelial cell interactions through a physiochemical barrier consisting of a family of glycoproteins referred to as mucins. Mucins provide an effective barricade restrict...

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Section: Discussionmentioning

confidence: 99%

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Coats

Hashim

Paramonov

et al. 2016

Appl Environ Microbiol

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“…LBP and sCD14 are reported to function as molecules that shuttle LPS, having both activatory and suppressive effects via mCD14 activation and HDL-mediated clearance, respectively (35,70). Very recently, a higher LBP/sCD14 ratio has been observed in patients suffering from gut-derived inflammation compared with controls (37).…”

Section: E380 Oil Composition and Endotoxin Receptorsmentioning

confidence: 99%

Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice

Laugerette

Furet

Debard

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

148

141

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Low-grade inflammation observed in obesity is a risk factor for cardiovascular disease. Recent studies revealed that this would be linked to gut-derived endotoxemia during fat digestion in high-fat diets, but nothing is known about the effect of lipid composition. The study was designed to test the impact of oil composition of high-fat diets on endotoxin metabolism and inflammation in mice. C57/Bl6 mice were fed for 8 wk with chow or isocaloric isolipidic diets enriched with oils differing in fatty acid composition: milk fat, palm oil, rapeseed oil, or sunflower oil. In vitro, adipocytes (3T3-L1) were stimulated or not with lipopolysaccharide (LPS; endotoxin) and incubated with different fatty acids. In mice, the palm group presented the highest level of IL-6 in plasma ( P < 0.01) together with the highest expression in adipose tissue of IL-1β and of LPS-sensing TLR4 and CD14 ( P < 0.05). The higher inflammation in the palm group was correlated with a greater ratio of LPS-binding protein (LBP)/sCD14 in plasma ( P < 0.05). The rapeseed group resulted in higher sCD14 than the palm group, which was associated with lower inflammation in both plasma and adipose tissue despite higher plasma endotoxemia. Taken together, our results reveal that the palm oil-based diet resulted in the most active transport of LPS toward tissues via high LBP and low sCD14 and the greatest inflammatory outcomes. In contrast, a rapeseed oil-based diet seemed to result in an endotoxin metabolism driven toward less inflammatory pathways. This shows that dietary fat composition can contribute to modulate the onset of low-grade inflammation through the quality of endotoxin receptors.

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“…Lakatos, et al investigated the association between serum level of LBP and sCD14 with clinical disease activity and they suggested both as markers of disease activity in CD with accuracy similar to that of hs-CRP [60].…”

Section: Lipopolysaccharide-binding Protein (Lbp) and Soluble Cd14 (Smentioning

confidence: 99%

Bio-Markers of Inflammatory Bowel Disease: Past, Present, and Future

Bahgat¹

2017

Austin J Gastroenterol

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Ulcerative colitis (UC) and Crohn's disease (CD) exemplify the two main arms of the spectrum of an idiopathic chronic disease known as inflammatory bowel disease (IBD). To date, this disease remained a puzzling dilemma in many aspects; including difficulties in its etiology/pathogenesis, diagnosis, severity assessment, treatment and outcomes/complications. Physicians usually get the diagnosis of IBD through a combination of clinical features, laboratory tests, radiology, as well as the invasive technique of endoscopy/biopsy. In spite of these efforts, the definite diagnosis can't be established in a significant cohort of cases. This paved the way to searching for laboratory biomarkers that are noninvasive, reproducible, rapid and relatively cheap than other modalities. Unfortunately, we're still far from these ideal biomarkers. Some biomarkers are already being used in daily practice including C-reactive protein (CRP) and fecal calprotectin while others are still in need for confirmation before being applied in clinical practice. In this review article, the authors are going to discuss the past, present, and future utility of biomarkers in IBD. This article aims at highlighting the uses and limitations of all possible current and novel biomarkers in every aspect of the disease from predisposition to prognosis.

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Serum lipopolysaccharide-binding protein and soluble CD14 are markers of disease activity in patients with Crohnʼs disease

Abstract: Serum LBP and sCD14 are markers of disease activity in CD with a similar accuracy as hs-CRP. In addition, LBP, sCD14, and a high frequency of previous relapses were independent predictors for 1-year clinical flare-up. (Inflamm Bowel Dis 2011).

Cited by 72 publications

References 39 publications

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice

Bio-Markers of Inflammatory Bowel Disease: Past, Present, and Future

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