Inhibition of lipopolysaccharide-induced release of interleukin-8 from intestinal epithelial cells by SMA, a novel inhibitor of sphingomyelinase and its therapeutic effect on dextran sulphate sodium-induced colitis in mice

Sakata, Akira; Yasuda, Kazuya; Ochiai, Takashi; Shimeno, Hiroshi; Hikishima, Sadao; Yokomatsu, Tsutomu; Shibuya, Shiroshi; Soeda, Shinji

doi:10.1016/j.cellimm.2007.03.005

Cited by 37 publications

(32 citation statements)

References 35 publications

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“…In addition, NO production in response to low and high doses of LPS remained unchanged under the influence of an NSMase inhibitor or NSMase gene silencing. When trying to explain the discrepancies between our results and those of earlier studies suggesting a positive influence of NSMasegenerated ceramide on expression of inducible NO-synthase and IL-8 production in LPS-stimulated cells (28)(29)(30), one should bear in mind that those studies were based solely on application of poorly characterized inhibitors of NSMase.…”

contrasting

confidence: 89%

“…To our knowledge, only a few earlier reports addressed the role of NSMase in regulation of IL-8 release (28) and expression of inducible NO-synthase (29,30) in LPS-stimulated epithelial cells, glioma cells, and macrophages, respectively. The studies were based on application of then newly synthesized inhibitors of NSMase and indicated a positive role of the NSMase-generated ceramide in cell reaction to LPS.…”

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confidence: 99%

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Ceramide and Ceramide 1-Phosphate Are Negative Regulators of TNF-α Production Induced by Lipopolysaccharide

Józefowski

Czerkies

Łukasik

et al. 2010

The Journal of Immunology

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LPS is a constituent of cell walls of Gram-negative bacteria that, acting through the CD14/TLR4 receptor complex, causes strong proinflammatory activation of macrophages. In murine peritoneal macrophages and J774 cells, LPS at 1–2 ng/ml induced maximal TNF-α and MIP-2 release, and higher LPS concentrations were less effective, which suggested a negative control of LPS action. While studying the mechanism of this negative regulation, we found that in J774 cells, LPS activated both acid sphingomyelinase and neutral sphingomyelinase and moderately elevated ceramide, ceramide 1-phosphate, and sphingosine levels. Lowering of the acid sphingomyelinase and neutral sphingomyelinase activities using inhibitors or gene silencing upregulated TNF-α and MIP-2 production in J774 cells and macrophages. Accordingly, treatment of those cells with exogenous C8-ceramide diminished TNF-α and MIP-2 production after LPS stimulation. Exposure of J774 cells to bacterial sphingomyelinase or interference with ceramide hydrolysis using inhibitors of ceramidases also lowered the LPS-induced TNF-α production. The latter result indicates that ceramide rather than sphingosine suppresses TNF-α and MIP-2 production. Of these two cytokines, only TNF-α was negatively regulated by ceramide 1-phosphate as was indicated by upregulated TNF-α production after silencing of ceramide kinase gene expression. None of the above treatments diminished NO or RANTES production induced by LPS. Together the data indicate that ceramide negatively regulates production of TNF-α and MIP-2 in response to LPS with the former being sensitive to ceramide 1-phosphate as well. We hypothesize that the ceramide-mediated anti-inflammatory pathway may play a role in preventing endotoxic shock and in limiting inflammation.

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confidence: 89%

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confidence: 99%

Ceramide and Ceramide 1-Phosphate Are Negative Regulators of TNF-α Production Induced by Lipopolysaccharide

Józefowski

Czerkies

Łukasik

et al. 2010

The Journal of Immunology

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“…CgA was the first granin to be characterized as an acidic protein co-stored and co-released with catecholamine hormones from the bovine adrenal medulla; CgA is also expressed by several other neuroendocrine cells, including cells of the gastroenteropancreatic endocrine system. Intracellular processing of CgA originates several peptides which display a wide range of biological activities [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], and VS-1 is one of these peptides. One of the effects of VS-1 is to protect the integrity of endothelial barriers.…”

Section: Discussionmentioning

confidence: 99%

“…We tested the effect of VS-1 on LPS-induced IL-8 production, an inflammatory chemokine that has been shown to be elevated in patients with IBDs, and suggested to play a role in the disease pathogenesis [35][36][37]. For this purpose, T-84 IECs (Fig.…”

Section: Vs-1 Inhibits Lps-induced Il-8 Productionmentioning

confidence: 99%

“…6a-c. Of note, sandwich ELISAs based on different antibodies against different epitopes detected different levels of VS-1 antigen in tissue extracts. In particular an ELISA assay based on the combination of mAb 5A8 (recognizing CgA epitope 54-57) and mAb 7D1 (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) gave higher values compared to the combination of mAb 5A8 and mAb B4E11 (epitope 68-71) indicating that fragments encompassing amino acids 34-57 were more abundant than fragments encompassing amino acids 54-71. To evaluate plasma levels of VS-1 or fragments thereof after systemic delivery, we administered, intraperitoneally, 3 lg of VS-1 to mice and measured VS-1 plasmatic levels using the ELISA based on mAb 5A8 and B4E11.…”

Section: Vs-1 or Fragments Thereof Can Be Recovered From The Gastroinmentioning

confidence: 99%

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The N-Terminal Fragment of Chromogranin A, Vasostatin-1 Protects Mice From Acute or Chronic Colitis Upon Oral Administration

et al. 2012

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Background Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), decreases the permeability of endothelial cells in vitro and in vivo. Aims Here, we investigated whether a similar effect could be observed also on intestinal epithelial cells (IECs) in vitro and whether VS-1 could have favorable effects on animal models of acute or chronic colitis, which are characterized by increased permeability of the intestinal epithelium. Methods In vitro, VS-1 was tested on IEC monolayers showing increased permeability, on mechanically injured IEC monolayers, and on the production of the chemokine IL-8/KC by lipopolysaccharide (LPS)-stimulated IECs. In vivo, VS-1 was tested in animal models of dextran sodium salt (DSS)-induced acute or chronic colitis.

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Sphingomyelin and phosphatidylcholine contrarily affect the induction of apoptosis in intestinal epithelial cells

Leucht

Fischbeck

Caj

et al. 2013

Molecular Nutrition Food Res

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Dietary phospholipids may induce or abolish apoptosis in IECs and seem to play a role in the pathogenesis of inflammatory bowel diseases. This nutritional factor might be considered when evaluating the pathogenesis of inflammatory bowel diseases. Effects of SMase- and SM treatment on inflammation in dextran sulfate sodium induced animal models of colitis and in vitro experiments are discussed as controversial. Variable sources of SM, feeding techniques, and mouse strains might play a role.

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Inhibition of lipopolysaccharide-induced release of interleukin-8 from intestinal epithelial cells by SMA, a novel inhibitor of sphingomyelinase and its therapeutic effect on dextran sulphate sodium-induced colitis in mice

Cited by 37 publications

References 35 publications

Ceramide and Ceramide 1-Phosphate Are Negative Regulators of TNF-α Production Induced by Lipopolysaccharide

Ceramide and Ceramide 1-Phosphate Are Negative Regulators of TNF-α Production Induced by Lipopolysaccharide

The N-Terminal Fragment of Chromogranin A, Vasostatin-1 Protects Mice From Acute or Chronic Colitis Upon Oral Administration

Sphingomyelin and phosphatidylcholine contrarily affect the induction of apoptosis in intestinal epithelial cells

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