Differential induction of IL-1 beta and IL-6 production by the nontoxic lipid A from Porphyromonas gingivalis in comparison with synthetic Escherichia coli lipid A in human peripheral blood mononuclear cells.
Porphyromonas gingivalis 381 lipid A possesses 1-phospho beta(1-6)-linked glucosamine disaccharide with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively. P. gingivalis lipid A indicated lower activities in inducing interleukin-1 beta (IL-1 beta) mRNA expression, pro-IL-1 beta protein synthesis and IL-1 beta production than those of synthetic Escherichia coli lipid A (compound 506) in human peripheral blood mononuclear cells (PBMC). The induction of IL-6 mRNA and IL-6 synthesis by P. gingivalis lipid A were comparable to those of compound 506. Herbimycin A, H-7 and H-8, inhibitors of tyrosine kinase, protein kinase C and cyclic nucleotide-dependent protein kinase, inhibited P. gingivalis lipid A- and compound 506-induced IL-1 beta and IL-6 synthesis. W-7, an inhibitor of calmodulin (CaM) kinase, inhibited only P. gingivalis lipid A-induced IL-1 beta production. The result suggests that the CaM kinase-dependent cascade is involved in the down-regulation of IL-1 beta production by P. gingivalis lipid A. P. gingivalis lipid A and compound 506 also functioned in the induction of tyrosine and serine/threonine phosphorylation of several proteins in PBMC. P. gingivalis lipid A inhibited specific binding of fluorescein-labelled E. coli LPS to the PBMC. The nontoxic lipid A of P. gingivalis, having a chemical structure different from toxic compound 506, appears to induce the up- and down-regulation of the differential cytokine-producing activities following the activation of various intracellular enzymes including the CaM kinase through the common receptor sites of LPS.
Ogawa
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T
Department of Oral Microbiology, Osaka University, Faculty of Dentistry, Japan.
Uchida
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H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D016227:Benzoquinones; D015152:Blotting, Northern; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D047029:Lactams, Macrocyclic; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008050:Lipid A / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D015394:Molecular Structure; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D047029:Lactams, Macrocyclic; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D011809:Quinones; D012333:RNA, Messenger; D013449:Sulfonamides; D017828:Rifabutin; C017967:W 7; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases