Insight into some of the signaling pathways triggered by a lipid immunomodulator.
The use of non specific immunomodulatory agents takes an important place in the aspecific host response to invading microorganisms. In this context, antimicrobial properties of royal jelly have been ascribed to organic acids (mainly 10 hydroxy-2-decenoic acid or 10-HDA) and proteins. We synthesized a derivative of 10-HDA, the 1-(2-methoxyethoxymethyl)2,3-(10-hydroxy2-decenoyl)(E) glycerol referred as diHDA-glycerol which was previously found to protect mice against virulent Salmonella typhimurium challenge through more adequate immune regulations. This study was conducted to further investigate some of the signaling pathways followed by diHDA-glycerol in cell transduction. Members of NF-kappaB transcription factors are key regulators of many cytokines acting on immunity and they control genes involved in responses to numerous signals such as bacterial products. Therefore, we investigated some parameters acting on NF-kappaB translocation in U937 cells after diHDA-glycerol treatment. Due to the chemical structure of the molecule we also investigated the sphingomyelinase pathway. Our results showed that diHDA-glycerol induced a rapid NF-kappaB translocation as a consequence of IkappaB-alpha proteolysis. An intracellular production of reactive oxygen species (ROS) may also account for NF-kappaB activation, without de novo protein synthesis. DiHDA-glycerol induced a strong activation of neutral sphingomyelinase, suggesting an important role of sphingolipids in the regulatory responses induced by diHDA-glycerol.
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Centre de Recherches du Service de Santé des Armées Emile Pardé, 24 avenue des Maquis du Grésivaudan, 38702 La Tronche cedex, France.
Bottex-Gauthier
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Li
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Potier
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Favier
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Vidal
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport; D003513:Cycloheximide / Q000494:pharmacology; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D020298:U937 Cells
C421303:1-(2-methoxyethoxymethyl)-2,3-(10-hydroxy-2-decenoyl)glycerol; D000276:Adjuvants, Immunologic; D000975:Antioxidants; D005995:Glyceryl Ethers; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D003513:Cycloheximide; D013108:Sphingomyelin Phosphodiesterase