Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts

Pfeiffer, Alexandra; Böttcher, Alfred; Orsó, Evelyn; Kapinsky, Michael; Nagy, Péter; Bodnár, Andrea; Spreitzer, Ingo; Liebisch, Gerhard; Drobnik, Wolfgang; Gempel, Klaus; Horn, Markus; Holmer, Stefan; Hartung, Thomas; Multhoff, Gabriele; Schütz, Gerhard J.; Schindler, Hansgeorg; Ulmer, Artur J.; Heine, Holger; Stelter, Felix; Schütt, Christine; Rothe, Gregor; Szöllősi, János; Damjanovich, Sándor; Schmitz, Gerd

doi:10.1002/1521-4141(200111)31:11<3153::aid-immu3153>3.0.co;2-0

Cited by 327 publications

(212 citation statements)

References 31 publications

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“…If milk SM were hydrolyzed by SMase and ceramidase to ceramide and sphingosine, respectively, each of those products could potentially exert anti-inflammatory effects. Longer-chain ceramides may compete with LPS and block TLR4 signaling, as they have been shown to bind to CD14 in monocytes and form a multi-molecular complex that contains CD36, but lacks TLR4 [57]. To confirm this, ceramides containing different amide-linked fatty acid chain lengths (16:0 and 24:0) and sphingoid bases (dihydroceramides) were tested.…”

Section: Discussionmentioning

confidence: 99%

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

et al. 2017

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High-fat diets (HFD) increase lipopolysaccharide (LPS) activity in the blood and may contribute to systemic inflammation with obesity. We hypothesized that dietary milk sphingomyelin (SM), which reduces lipid absorption and colitis in mice, would reduce inflammation and be mediated through effects on gut health and LPS activity. C57BL/6J mice were fed high-fat, high-cholesterol diets (HFD, n = 14) or the same diets with milk SM (HFD-MSM, 0.1% by weight, n = 14) for 10 weeks. HFD-MSM significantly reduced serum inflammatory markers and tended to lower serum LPS (p = 0.08) compared to HFD. Gene expression related to gut barrier function and macrophage inflammation were largely unchanged in colon and mesenteric adipose tissues. Cecal gut microbiota composition showed greater abundance of Acetatifactor genus in mice fed milk SM, but minimal changes in other taxa. Milk SM significantly attenuated the effect of LPS on pro-inflammatory gene expression in RAW264.7 macrophages. Milk SM lost its effects when hydrolysis was blocked, while long-chain ceramides and sphingosine, but not dihydroceramides, were anti-inflammatory. Our data suggest that dietary milk SM may be effective in reducing systemic inflammation through inhibition of LPS activity and that hydrolytic products of milk SM are important for these effects.

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Section: Discussionmentioning

confidence: 99%

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

et al. 2017

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“…This interaction between Syk and TLR4 seen in neutrophils at baseline and upon LPS stimulation may be direct or indirect. Previously Syk has been shown to associate with CD18 and the Fc␥ receptor, both of which interact with TLR4 upon LPS stimulation in macrophages, which suggests an indirect association of Syk with TLR4 (61,74,75). In support of a direct association of Syk with TLR4, TLR4 contains a motif in the intracytoplasmic portion that is a putative Syk-SH2 domain recognition site, suggesting that Syk may associate with TLR4 directly through this domain (76).…”

Section: Sp600125 Does Not Inhibit Lps-induced Syk Phosphorylation-mentioning

confidence: 90%

Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils

Arndt

Suzuki

Avdi

et al. 2004

Journal of Biological Chemistry

140

135

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“…Integrins (␣4␤7 integrin) are involved in tissue homing of mast cells 92 and CD14 plays a major role in the inflammatory response induced by LPS. 93 Furthermore, LPS significantly induced CD14 mRNA expression. 94 A possible explanation for the down-regulation is that during chronic inflammation, inhibitory feedback mechanisms would decrease the expression of CD14, integrin, and MMP11.…”

Section: Acute and Chronic Inflammationmentioning

confidence: 91%

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

Saban

Nguyen

Hammond

et al. 2002

The American Journal of Pathology

110

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Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and isClinical and animal models of acute and chronic urinary bladder inflammation have provided several lines of evidence suggesting a central role of mast cells, sensory nerves, and neurokinin (NK)-1 receptors. Fundamental work regarding the participation of sensory nerves and mast cells in cystitis provides indirect evidence, such as increased numbers of mast cells in the detrusor and submucosa, and morphological evidence of mast cell activation and degranulation. [1][2][3][4] In addition, the extensive tissue remodeling seen in some clinical forms of bladder inflammation such as interstitial cystitis, 4 along with increased urinary levels of histamine and tryptase 5 suggest a role for mast cells. Because both mast cells 6 -8 and NK-1 receptors are increased in bladder biopsies of interstitial cystitis (IC) patients, 9,10 it is tempting to propose a role for sensory peptides-mast cell communication in the pathogenesis of this disorder.Experimentally, we have used classical morphometric analysis and microarray technology to determine the role of mast cells, NK-1 receptors, and bacterial toxins in animal models of cystitis. Time-course experiments indicated early and late genes involved in bladder inflammatory responses. 11 The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R Ϫ/Ϫ ) allowed us to propose a mandatory role of SP receptors in cystitis. 12 We also determined genes that depend on the presence of tissue mast cells for their expression by comparing inflammatory responses in mast cell-deficient (Kit W /

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Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts

Cited by 327 publications

References 31 publications

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

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