Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of 27 tropolones on nitric oxide (NO) production by mouse macrophage-like Raw 264.7 cells. All of these compounds failed to stimulate the Raw 264. 7 cells to produce detectable amounts of NO, but inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. Generally, the ability of tropolones to inhibit LPS-stimulated NO production was inversely related to their cytotoxic activity. Western blot and RT-PCR analyses demonstrated that the most active compound, 2,4-dibromo-7-methoxytropone [21], significantly reduced both the intracellular concentration of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that [21] did not produce radicals under alkaline condition, nor scavenged NO, produced by NOC-7. These data suggested that the inhibitory effect of [21] on NO production might be generated via the inhibition of iNOS expression, rather than a radical-mediated mechanism.
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PMID:Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by tropolones. 1573 32

We investigated the effect of twenty-seven azulenes on nitric oxide (NO) production by mouse macrophage-like Raw 264.7 cells. No azulene derivative alone induced NO production by the Raw 264.7 cells, but inhibited lipopolysaccharide (LPS)-stimulated NO production to various extents. The ability of azulenes to inhibit NO generation by activated macrophages was generally increased when their cytotoxic activity declined. Western blot and RT-PCR analyses demonstrated that the most potent compound, 1,3-difluoroazulene [11], slightly inhibited the expression of inducible NO synthase (iNOS), but only at extremely high concentrations. ESR spectroscopy showed that [11] did not produce radical under alkaline condition, nor scavenged O2- (generated by HX-XOD reaction) or NO (generated by NOC-7). These data suggest that the inhibitory effect of [11] may be produced via a mechanism other than iNOS induction and a radical-mediated mechanism.
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PMID:Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by azulenes. 1573 35

Rikko-san and its ingredients were investigated for their activity to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. LPS significantly stimulated the NO production by Raw 264.7 cells, and Rikko-san effectively inhibited the stimulation effect of LPS even at non-cytotoxic concentrations. Among 5 Rikko-san ingredients, Kanzo showed a similar magnitude of inhibition of NO production. Shoma was also slightly inhibitory. On the other hand, Ryutan, Saishin and Bofu did not show such a clear-cut stimulation effect, due to the co-existence of both inhibitory and stimulatory substance(s) for NO production. Thus NO stimulators were present in Rikko-san and its four ingredients except for Kanzo. Western blot analysis demonstrated that LPS induced the production of inducible NO synthase (iNOS), and that non-cytotoxic concentrations of Rikko-san and Kanzo significantly inhibited the LPS-stimulated iNOS expression. ESR spectroscopy showed that Rikko-san, Kanzo, Shoma and Saishin, but not Ryutan and Bofu, produced radical(s) under alkaline condition. All samples scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7)), possibly by their general reducing activity. These data suggest that the inhibition of NO production by Chinese medicines investigated here may be the result of both the inhibition of iNOS expression and their radical scavenging activity.
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PMID:Inhibition by Rikko-san and its major ingredients of LPS-stimulated nitric oxide production by mouse macrophage-like cells. 1579 69

The effect of Cu plate on the cellular function was investigated by two different methods: an extraction method (Method I) and a direct contact method (Method II). In Method I, the supernatant of the culture medium, which had been pre-incubated with Cu plate, was added to mouse macrophage-like Raw 264.7 cells. This supernatant dose-dependently inhibited the proliferation and nitric oxide (NO) production by lipopolysaccharide-stimulated Raw 264.7 cells. In Method II, human promyelocytic leukemic HL-60 cells in suspension were incubated with culture medium which contained Cu plate. The direct contact with Cu plate rapidly suppressed the proliferation and MnSOD and Cu/ZnSOD activities. The suppressed proliferation and SOD activity reverted to or exceeded the control level by sodium ascorbate, whereas N-acetyl-L-cysteine (NAC) only reactivated the proliferation, but not the SOD activity. ESR spectroscopy showed that contact with Cu plate slightly diminished the hydroxyl radical (generated by Fenton reaction), without affecting the intensity of NO (produced from NOC-7) and DPPH radical. The present study suggests that two representative antioxidants, such as sodium ascorbate and NAC, protect the cells from Cu-induced cytotoxicity via different mechanisms.
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PMID:Protection by antioxidants of copper-induced decline of proliferation and SOD activity. 1581 49

Azulenequinone derivatives have been reported to display a broad spectrum of biological activities, but study at the cellular level has been limited. The effect of twenty-seven azulenequinone derivatives on nitric oxide (NO) production by mouse macrophage-like cells Raw 264.7 was investigated in this study. All of these compounds failed to stimulate the Raw 264.7 cells to produce detectable amounts of NO, but did inhibit NO production by lipopolysaccharide (LPS)-activated Raw 264. 7 cells to varying extents. Compounds [7, 8, 9, 13, 16, 25, 27], which showed lesser cytotoxic activity (CC50 = 425, 381, 482, 179, 119, 235, 225 microM, respectively), inhibited NO production to the greatest extent [selectivity index (SI) = 15.4, 26.2, 3.9, 21.6, 3.1, 6.0, 8.4, respectively]. Western blot and RT-PCR analyses demonstrated that the most active derivatives, 3-morpholino-1, 5-azulenequinone [8] and 3,7-dibromo-1, 5-azulenequinone [13], significantly reduced both the intracellular concentration of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that compounds [8, 13] weakly scavenged NO produced by NOC-7, possibly via their general reducing activity. These data suggest that the inhibitory effect of NO production by compounds [8, 13] might be generated mostly via the inhibition of iNOS expression, rather than the radical-mediated mechanism.
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PMID:Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by azulenequinones. 1630 11

The effects of 26 trihaloacetylazulene derivatives on nitric oxide (NO) production by the mouse macrophage-like Raw 264.7 cells was investigated. The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared with the corresponding trifluoroacetylazulenes [1a-13a]. All the compounds inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. 3-Trifluoroacetylguaiazulene [8a], 1-trifluoroacetyl-4,6,8-trimethylazulene [10a], 3-methyl-l-trichloroacetylazulene [2b] and 3-ethyl-1-trichloroacetylazulene [3b] showed lower cytotoxic activity and most effectively inhibited NO production. Western blot analysis revealed that compounds [8a, 1Oal dose-dependently reduced the intracellular concentration of inducible NO synthase (iNOS), whereas compounds [2b, 3b] only marginally affected the iNOS protein expression. RT-PCR analysis showed that compounds [8a, 2b] reduced the iNOS mRNA expression by approximately 50%. These compounds affected cyclooxygenase-2 protein and mRNA expression, depending on the concentrations. ESR spectroscopy revealed that compounds [8a, 10a, 2b, 3b] neither produced radical, nor scavenged NO, superoxide anion or diphenyl-2-picrylhydrazyl radicals. The present study showed the inhibitory effects of trifluoroacetylazulenes and trichloroacetylazulenes on NO production by activated macrophages.
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PMID:Inhibition of NO production in LPS-stimulated mouse macrophage-like cells by trihaloacetylazulenes. 1688 14

In this work the attempt to estimate a nitric oxide (NO*) role in regulation of the number of pool haemopoietic stem cells at the irradiated mice was made. With this purpose the number of new compounds from dihydrothiazine-thiazoline line was synthesized, their NO-inhibiting activity was investigated in vivo by the method of ESR-spectroscopy of spin trap and their influence on an output endogenous spleen colonies (CFU-S-8) after the total sublethal y-irradiation of mice in a doze of 6 Gy was also investigated. Was shown, that the tested compounds reduced the contents of NO* in a liver tissue of mice which have received an injection of nitric oxide synthesis inductor - lipopolysaccharide, and also increased an output CFU-S-8 forming endogenous colonies in the spleen of the irradiated mice. Received data testify to perceptivity of search radioprotective agents among NO* synthesis inhibitors.
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PMID:[The influence of some retarding agents NOS of dihydrothiazine-thiazoline rank on postradiational of recovery endogenous CFU-S-8 of mice]. 1738 89

Two transformed murine macrophage cell lines (RAW 264.7 ATCC TIB-71 and CRL-2278) were examined for oxidant production at various times following activation by using a set of fluorescence and ESR-active probes. Stimulation with a soluble agonist or activation with bacterial lipopolysaccharide plus gamma-interferon caused only very small initial increases in O2 consumption above basal rates; however, at 2-4 h post-activation, respiration increased to 2-3-fold and remained at these elevated levels over the subsequent lifetime of the cell (20-30 h). Oxidation reactions were confined primarily within the cell, as was demonstrated by using phagocytosable dichlorodihydrofluorescein-conjugated latex beads and cyclic hydroxylamines with differing membrane permeabilities. From the intrinsic reactivities of these probes and the time course of their oxidations, one infers the induction of apparent peroxidase activity beginning at approximately 2 h post-activation coinciding with the increase in overall respiratory rate; this acquired capability was accompanied by accumulation of a stable horseradish peroxidase-reactive oxidant, presumably H2O2, in the extracellular medium. Nitrite ion rapidly accumulated in the extracellular medium over a period of 5-8 h post-activation in both cell lines, indicating the presence of active nitric oxide synthase (iNOS) during that period. Prostaglandin endoperoxide H synthase (COX-2) activity was detected at 15-20 h post-activation by the use of a sensitive peroxide assay in conjunction with a COX-2 specific inhibitor (DuP-697). Superoxide formation was detected by reaction with hydroethidine within the first hour following activation, but not thereafter. Consistent with the absence of significant respiratory stimulation, the amount of O2*- formed was very small; comparative reactions of cyclic hydroxylamine probes indicated that virtually none of the O2*- was discharged into the external medium. Myeloperoxidase (MPO) activity was probed at various times post-activation by using fluorescein-conjugated polyacrylamide beads, which efficiently trap MPO-generated HOCl in neutrophils to give stable chlorofluorescein products. However, chlorination of the dye was not detected under any conditions in RAW cells, virtually precluding MPO involvement in their intracellular reactions. This same probe was used to determine changes in intraphagosomal pH, which increased slowly from approximately 6.5 to approximately 8.2 over a 20 h post-phagocytosis period. The cumulative data suggest that activation is followed by sequential induction of an endogenous peroxidase, iNOS, and COX-2, with NADPH oxidase-derived O2*- playing a minimal role in the direct generation of intracellular oxidants. To account for reported observations of intracellular tyrosine nitration late in the life cycles of macrophages, we propose a novel mechanism wherein iNOS-generated NO2- is used by COX-2 to produce NO2* as a terminal microbicidal oxidant and nitrating agent.
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PMID:Pathways for intracellular generation of oxidants and tyrosine nitration by a macrophage cell line. 1753 Aug 64

Twenty-six benzocycloheptoxazine derivatives were investigated for their effect on nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. Benzo[b]cyclohepta[e][1,4]thiazine most effectively inhibited the LPS-stimulated NO production at noncytotoxic concentrations. 6H-Benzo[b]cyclohepta[e][1,4]-diazine cation, and benzo[b]cyclohepta[e][1,4]oxazine and its 6-bromo derivative also efficiently inhibited the LPS-stimulated NO production. Another sixteen benzo[b]cyclohepta[e]-[1,4]oxazine derivatives, 14H-[1,4]benzoxazino[3',2' :3,4]-cyclohepta[1,2-b][1,4]benzoxazine and its 7-bromo- and 7-isopropyl derivatives were slightly less active (selectivity index (SI)=83-66). Bromination of benzo[b]cyclohepta[e][1,4]-thiazine, benzo[b]cyclohepta[e][1,4]oxazine and 2-methylbenzo[b]cyclohepta[e][1,4]oxazine at C-6, C-8 or C-10 positions resulted in the significant reduction of the inhibitory activity. The observed inhibitory activity of benzo[b]cyclohepta-[e][1,4]thiazine and its 6,8-dibromo derivatives were not due to the reduction of the intracellular level of inducible NO synthase protein (based on Western blot analysis), nor to NO scavenging activity (based on ESR spectroscopy). These results suggest the possible anti-inflammatory action of benzocyclo-heptoxazines via inhibition of LPS-activated macrophages.
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PMID:Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by benzocycloheptoxazines. 1903 91

Mastic is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. Mastic has shown several beneficial pharmaceutical properties such as antibacterial and apoptosis-modulating activities. The aim of this study was to investigate whether mastic affects the function of activated macrophages. Both solid and liquid types of mastic inhibited the production of pro-inflammatory substances such as nitric oxide (NO) and prostaglandin (PG)E(2) by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells. This was accompanied by the decline of viable cell number. Western blot and RT-PCR analyses showed that mastic inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at both protein and mRNA levels. ESR spectroscopy revealed that mastic scavenged NO and superoxide radicals very poorly, in contrast to its potent hydroxyl radical scavenging activity. These data demonstrate that mastic inhibits the production of both NO and PGE(2) by activated macrophages mostly via its cytotoxic action. The narrow range of effective concentration of mastic due to its cytotoxicity may limit its potential application as an anti-inflammatory agent.
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PMID:Re-evaluation of anti-inflammatory activity of mastic using activated macrophages. 1956 94


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