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1.
Glucocorticoid inhibition of adjuvant arthritis synovial macrophage nitric oxide production: role of lipocortin 1
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Nitric oxide (NO) is a mediator of inflammatory injury which is inhibited by glucocorticoids and is implicated in rheumatoid (RA) and adjuvant arthritis (AA). The glucocorticoid-induced anti-inflammatory molecule lipocortin 1 is expressed in RA synovium, but the effects of lipocortin 1 on synovial inflammation have been little studied. We investigated the effects of glucocorticoids and lipocortin 1 on inducible NO synthase (iNOS) and glucocorticoids on the induction of lipocortin 1 in AA synovial macrophages. NO production was measured by Griess assay in supernatants of day 14 AA rat synovial explants and of synovial macrophages purified from enzyme-digested synovium and treated with lipopolysaccharide (LPS) 1 μg/ml, dexamethasone (DEX) 10?7 M , and anti-lipocortin 1 MoAb. iNOS and lipocortin 1 expression were detected by flow cytometry using specific MoAb. Cell surface lipocortin was determined by Western blot. NO was produced by all AA synovial explants and NO was released by cultured synovial macrophages (14.5 ± 2.1 μmol/24 h). iNOS was detected in synovial macrophages (ED-1+) by permeabilization flow cytometry. LPS increased synovial macrophage NO release (P < 0.0001) and iNOS expression (P = 0.04). DEX inhibited constitutive (P = 0.002) and LPS-induced (P < 0.001) NO release and iNOS expression (P = 0.03). DEX inhibition of synovial macrophage NO was associated with induction of cell surface and intracellular lipocortin 1. Anti-lipocortin 1 MoAb treatment reduced the inhibition of NO release by DEX (P = 0.002), but had no effect on iNOS expression. These findings demonstrate a role for lipocortin 1 in the inhibition by glucocorticoids of AA synovial macrophage iNOS activity. 相似文献
2.
一氧化氮对香烟烟雾提取物诱导大鼠肺泡巨噬细胞核因子кB活化的影响 总被引:2,自引:2,他引:2
目的:探讨一氧化氮(NO)对香烟烟雾提取物(CSE)诱导的大鼠肺泡巨噬细胞(AM)中核因子κB(NF—κB)活化的影响及机 制。方法:将大鼠AM与不同浓度的NO前体左旋精氨酸(L-Arg)或iNOS特异性抑制剂N6-(1-亚氨乙基)赖氨酸(L-NIL)及CSE共同培养,用免疫细胞化学染色法检测NF-κB,用Western blot检测I-κB蛋白含量,用Griess法测定培养上清液中NO的水平。结果:CSE可使NF-κB活化细胞的百分率增加,I-κB的水平下降。加入CSE和低浓度L-Arg培养的AM,NF-κB活化细胞的百分率显著高于只加入CSE的AM;而I-κB的水平显著低于只加入CSE的AM。加入CSE和高浓度L-Arg培养的AM,NF-κB活化细胞的百分率显著低于只加入CSE的AM,而I-κB的水平无显著变化。加入CSE和不同浓度的L-NIL培养的AM,NF-κB活化细胞的百分率显著低于只加入CSE的AM;而I-κB的水平则显著高于只加入CSE的AM,并呈浓度依赖(P<0.01)。结论:内源性NO对香烟烟雾所致NF-κB的活化具有双向调控作用。 相似文献
3.
目的:探讨一氧化氮(NO)对香烟烟雾提取物(CSE)诱导的大鼠肺泡巨噬细胞(AM)中核因子κB(NF—κB)活化的影响及机 制。方法:将大鼠AM与不同浓度的NO前体左旋精氨酸(L-Arg)或iNOS特异性抑制剂N6-(1-亚氨乙基)赖氨酸(L-NIL)及CSE共同培养,用免疫细胞化学染色法检测NF-κB,用Western blot检测I-κB蛋白含量,用Griess法测定培养上清液中NO的水平。结果:CSE可使NF-κB活化细胞的百分率增加,I-κB的水平下降。加入CSE和低浓度L-Arg培养的AM,NF-κB活化细胞的百分率显著高于只加入CSE的AM;而I-κB的水平显著低于只加入CSE的AM。加入CSE和高浓度L-Arg培养的AM,NF-κB活化细胞的百分率显著低于只加入CSE的AM,而I-κB的水平无显著变化。加入CSE和不同浓度的L-NIL培养的AM,NF-κB活化细胞的百分率显著低于只加入CSE的AM;而I-κB的水平则显著高于只加入CSE的AM,并呈浓度依赖(P<0.01)。结论:内源性NO对香烟烟雾所致NF-κB的活化具有双向调控作用。 相似文献
4.
目的探讨商业用腹膜透析液(commercial peritoneal dialysate,CDS)对腹腔巨噬细胞功能的影响.方法培养的小鼠腹腔巨噬细胞(Mφ)在含不同葡萄糖浓度(15、25和42 g/L)的CDS中,经不同时间(10、30和60 min)的暴露,观察MФ还原MTF的能力及其NO的产量.结果低葡萄糖浓度(25 g/L)暴露10 min实验组,MФ还原MTT的能力(A570nm值)为0.210±0.008,NO的产量为(9.1±1.3)μmol/L,均明显低于对照组(P<0.01);高葡萄糖浓度(42 g/L)和较长时间(60 min)暴露组,MФ还原MTF的能力(A570nm值)为0.056±0.004,NO的产量为(5.7±1.1)μmol/L,与对照组相比较,改变最明显(P<0.01).结论短时间CDS暴露,即可降低MФ的活力及NO产生,这种作用与CDS中的葡萄糖浓度以及MФ暴露于CDS的时间呈正相关. 相似文献
5.
一氧化氮在巨噬细胞的细胞毒效应中的作用 总被引:4,自引:0,他引:4
目的:探讨一氧化氮(NO)对巨噬细胞细胞毒效应的影响。方法:将20只昆明种小鼠分为两组,一组皮下接种S180横纹肌肉瘤细胞,另一组作为正常对照组。分别取两组小鼠腹腔灌洗液中的巨噬细胞与K562肿瘤细胞共同培养,检测在培养液中加入左旋精氨酸(L-Arg)和G-单甲基左旋精氨酸(L-NAME)后巨噬细胞杀伤率的改变。结果:正常小鼠腹腔灌洗液中的巨噬细胞在L-Arg和L-NAME存在的情况下细胞毒效应没有改变;荷瘤小鼠腹腔灌洗液中的巨噬细胞在L-Arg组和空白组中的细胞毒效应明显增强。结论:NO是巨噬细胞细胞毒作用的一个效应分子。 相似文献
6.
Zhai Z Haney D Wu L Solco A Murphy PA Wurtele ES Kohut ML Cunnick JE 《Food and Agricultural Immunology》2007,18(3-4):221-236
It has been suggested that Echinacea has anti-inflammatory activity in vivo. Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta are important mediators in the inflammatory response. The effect of alcohol extracts of E. angustifolia (EA), E. pallida (EPA) and E. purpurea (EP) on the production of these inflammatory mediators in both LPS-stimulated RAW 264.7 macrophages in vitro and murine peritoneal exudate cells (PECs) in vivo were investigated. As macrophages produce these inflammatory mediators in response to pathogenic infection, parallel cultures of macrophages were studied for phagocytosis and intracellular killing of Salmonella enterica. EPA and EP in vitro inhibited NO production and TNF-α release in a dose-dependent manner. RAW 264.7 cells treated with EA or EP showed decreased killing over 24 h, although EA enhanced bacterial phagocytosis. Upon bacterial infection, RAW 264.7 cells produce high levels of NO; however, an Echinacea-mediated decrease in NO production was observed. Echinacea alcohol extracts administered orally at 130 mg/kg per day for seven days had a weak effect on NO production and phagocytosis by LPS-stimulated PECs. The results indicated that all Echinacea species significantly decreased inflammatory mediators in vitro, however, only EA and EP reduced bacterial killing. Oral administration of Echinacea alcohol extracts did not adversely affect the development and anti-bacterial function of inflammatory PECs in vivo, however, NO production was decreased during bacterial infection of PECs. 相似文献
7.
The activation of macrophages for antimicrobial responses is a multistage event involving numerous intracellular signalling cascades that makes possible target cell destruction by these effector cells. This study examined the effects of different potassium channel inhibitors and activators on the NO production of murine macrophage-like cell lines P388D.1 and B10-4(S). We found that the potassium channel inhibitors tetraethylammonium, 4-aminopyridine, and quinine caused dose-dependent reductions in the NO production of macrophages, and that the potassium channel activator, minoxidol, caused a dose-dependent enhancement of NO production. The inhibition of NO production was due to involvement of potassium channels in the priming stage of macrophage activation, since pretreatment with the priming agent interferon-gamma partially restored the NO response of the macrophages. The results of this study demonstrate a link between potassium channel activity and the activation of anitimicrobial functions of murine macrophages. 相似文献
8.
Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide 总被引:4,自引:0,他引:4
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M. TOHYAMA K. KAWAKAMI M. FUTENMA A. SAITO 《Clinical and experimental immunology》1996,103(3):436-441
We examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-γ)-induced cryptococcostatic activity of murine peritoneal macrophages using NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of RNI synthesis, and superoxide dismutase (SOD) and catalase, oxygen radical scavengers. IFN-γ-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant. IFN-γ also enhanced the suppressive effect on cryptococcal growth in a similar dose-dependent manner. The induction of killing activity and NO production by an optimal dose of IFN-γ (100 U/ml) was virtually suppressed by 500 μM L-NMMA. These results confirmed the importance of the RNI-mediated effector mechanism in anticryptococcal activity of macrophages. SOD and catalase significantly enhanced the cryptococcostatic activity of macrophages induced by a suboptimal dose of IFN-γ (20 U/ml). The augmenting effect of these reagents was mediated by NO, since they potentiated the production of NO by macrophages and their effects were totally blocked by L-NMMA. Our results indicate that the IFN-γ-induced anticryptococcal activity of macrophages is dependent mostly on RNI, and suggest that the ROI system down-regulates the effector mechanism for cryptococcostasis by suppressing the RNI system. 相似文献
9.
Wang D Braendstrup O Larsen S Horn T Strandgaard S 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2004,112(6):358-368
Nitric oxide (NO) influences tubular fluid and electrolyte transport, and hence possibly also fluid accumulation in renal cysts. The expression and activity of intrarenal constitutive NO synthase (cNOS) [neuronal NOS, nNOS and endothelial NOS, eNOS] and inducible NOS (iNOS) and plasma nitrite/nitrate (PNOx) concentration were assessed in homozygous Han:SPRD polycystic kidney disease (PKD) rats (cy/cy), heterozygous Han:SPRD PKD rats (cy/+), homozygous normal Han:SPRD littermates (+/+) and Sprague Dawley rats (sd). The results showed: 1) nNOS expression was decreased in proximal tubules and thick ascending limbs of the loop of Henle in cy/cy and cy/+ rats compared to +/+ and sd rats (p<0.05). nNOS was weakly expressed in the epithelium of small cysts and unexpressed in epithelium of large cysts. 2) iNOS expression was increased in proximal tubular epithelial cells in cy/+ rats compared to +/+ rats and sd rats (p<0.01). iNOS expression in cyst epithelium was decreased in cy/+ rats (p<0.05) and absent in cy/cy rats. 3) eNOS expression was similar in the endothelium of intrarenal arteries in all groups. 4) The activity of renal cNOS was decreased in cy/cy and cy/+ rats; the activity of iNOS was decreased only in cy/cy rats, with no significant difference among the other three groups. 5) PNOx concentration was higher in cy/cy rats than in the other three groups, and correlated positively with plasma creatinine and urea. In conclusion, NOS expression and activity decreased as cysts developed, suggesting that NO downregulation is involved in the pathogenesis of PKD. 相似文献
10.
研究氨甲蝶呤(MTX)在小鼠巨噬细胞(RAW264.7)对一氧化氮合酶(NOS)表达的抑制作用。本试验应用内毒素(LPS)、干扰素(IFNr)、MTX、二氨基-羟基嘧啶(DAHP),四氢生物喋呤(BH4)刺激8h后,用Northern杂交检测NOS mRNA水平和GTP-CH-1 mRNA水平表达,并用Griess reaction方法检测NO2^-/NO3^-浓度,用Duch方法测定GTP-CH-1活性值。我们发现,MTX在小鼠巨噬细胞(RAW264.7)对NOS mRNA水平和GTP-HC-1 mRNA水平表达有轻度抑制作用,对NO2^-/NO3^-浓度和GTP-CH-1活性抑制作用较弱。MTX和DAHP联合应用不仅对NOS mRNA水平和GTP-CH-1 mRNA水平表达抑制作用较强,而且对NO2^-/NO3^-浓度和GTP-CH-1活性抑制较大。BH4的加入可以减少MTX和DAHP对一氧化氮(NO)生成的抑制作用。 相似文献
11.
目的 观察急性应激对大鼠血小板一氧化氮(NO)释放的影响及其机制.方法 大鼠浸水-束缚应激(WRS)2、4和8 h,以胃溃疡指数(UI)作为应激损伤的标识,采用Greiss法测定血小板孵育液中亚硝酸盐(NO2-)含量;同位素法测其一氧化氮合酶(NOS)活性和L精氨酸(L-Arg)转运量.结果 WRS 2 h血小板L-Arg转运量、NOS活性和孵育液NO2-含量较对照组显著增加,但随应激时间延长,其呈下降趋势,应激8 h时均显著低于对照组,胃溃疡逐渐加重.结论 WRS应激早期阶段可上调血小板L-Arg/NO通路,促进血小板NO生成;长时间应激下调L-Arg/NO通路,减少NO释放. 相似文献
12.
13.
《Journal of immunotoxicology》2013,10(4):393-400
AbstractMentha longifolia is an aromatic plant used in flavoring and preserving foods and as an anti-inflammatory folk medicine remedy. The present study assessed the effects of M. longifolia extracts, including essential oil and crude methanol extract and its fractions (ethyl acetate, butanol and hexane), on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression in lipopolysaccharide (LPS)-stimulated J774A.1 cells using real-time polymerase chain reaction (PCR). The cytotoxic effects of the extracts on the cells were examined and non-cytotoxic concentrations (<0.2?mg/ml) were used to examine their effects on NO production and iNOS mRNA expression. Only the hexane fraction that contained high levels of phenolic and flavonoid compounds at concentrations from 0.05–0.20?mg/ml significantly reduced NO production in LPS-stimulated cells (p?<?0.001). Real-time PCR analysis indicated the ability of this fraction at the same concentrations to significantly decrease iNOS as well as TNFα mRNA expression in the cells (p?<?0.001). All extracts were able to scavenge NO radicals in a concentration-dependent manner. At concentrations greater than 0.2?mg/ml, total radicals were 100% scavenged. In conclusion, M. longifolia possibly reduces NO secretion in macrophages by scavenging NO and inhibiting iNOS mRNA expression, and also decreases TNFα pro-inflammatory cytokine expression, thus showing its usefulness in the inflammatory disease process. 相似文献
14.
Malysheva EV Kruglov SV Khomenko IP Bakhtina LY Pshennikova MG Manukhina EB Malyshev IY 《Bulletin of experimental biology and medicine》2006,141(4):404-406
We studied the role of nitric oxide in the stress response and apoptosis. Intracellular nitric oxide potentiated the stress
response. However, intracellular nitric oxide suppressed the stress response in macrophages of proinflammatory and antiinflammatory
phenotypes. Intracellular nitric oxide promoted apoptosis in macrophages of the proinflammatory phenotype, but inhibited this
process in cells of the antiinflammatory phenotype. Exogenous nitric oxide synthesized by macrophages protected them from
lipopolysaccharide-induced apoptosis. Our results indicate that nitric oxide produces various effects on the stress response
and apoptosis in macrophages, which depends on modus operandi.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 386–388, April, 2006 相似文献
15.
溶血磷脂酰胆碱对内皮细胞一氧化氮的生成的影响 总被引:2,自引:0,他引:2
目的:探讨溶血磷脂酰胆碱(Lysophosphatidylcholine,Lyso-PC)对培养的人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)一氧化氮(nitric oxide,NO)的生成的影响。方法:采用NO酶法测定内皮细胞NO生成的变化。结果:内皮细胞NO的生成对Lyso-PC具有时间和剂量依赖性,结论:Lyso-PC可能通过抑制内皮细胞NO的生成而导致动脉粥样硬化损伤的形成。 相似文献
16.
Apigenin is a naturally occurring flavone isolated from the medicinal herb, Aster yomena. The present study was designed to elucidate the apoptosis-like antibacterial mechanism of apigenin in Escherichia coli. Administration of apigenin resulted in a rapid increase in intracellular calcium accompanied by an increase in reactive nitrogen species (RNS) and nitric oxide (NO) levels. Furthermore, apigenin increases reactive oxygen species (ROS), superoxide anion (O2–) which left E. coli with no ability to activate superoxide dismutase. Finally, we found that perturbance of the membrane lipid bilayer leading to glutathione oxidation and formation 8-hydroxy-2′-deoxyguanosine occurred during the process and apoptosis-like death hallmarks were further observed. Furthermore, we applied the NO synthase inhibitor ( l -NAME) and the O2– scavenger (Tiron) and observed attenuation in apoptotic markers under their presence. Taken together, these results suggest that apigenin induces bacterial apoptosis via activation of cellular oxidative pathways dependent on the production and accumulation of RNS/ROS. 相似文献
17.
18.
Nilsson MC Fredén F Wiklund P Hambraeus-Jonzon K 《Acta physiologica (Oxford, England)》2011,202(1):59-68
Aim: In the severely ill intensive care patients metabolic acidosis and hypoxia often co‐exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model. Methods: Eighteen healthy anaesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Six pigs received HCl infusion (HCl group), six pigs received the non‐specific NOS inhibitor Nω‐nitro‐l ‐arginine methyl ester (l ‐NAME) and HCl infusions (l ‐NAME + HCl group) and six pigs received buffered Ringer’s solution (control group). NO concentration in exhaled air (ENO), NOS activity in lung tissue, and regional pulmonary blood flow were measured. Results: Metabolic acidosis, induced by infusion of HCl, decreased the relative perfusion to the hypoxic LLL from 7 (3) [mean (SD)] to 3 (1) % in the HCl group (P < 0.01), and from 4 (1) to 1 (1) % in the l ‐NAME + HCl group (P < 0.05), without any measurable significant changes in ENO from hypoxic or HL regions There were no significant differences between the HCl and control groups for Ca2+‐dependent (cNOS) or Ca2+‐independent NOS (iNOS) activity in hypoxic or HL regions. Conclusions: Metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary NOS dependent or NOS independent NO production. When acidosis was induced during ongoing NOS blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis‐induced pulmonary vasoconstriction was not NO dependent. 相似文献
19.
Utaisincharoen P Anuntagool N Chaisuriya P Pichyangkul S Sirisinha S 《Clinical and experimental immunology》2002,128(3):467-473
Synthetic CpG containing oligodeoxynucleotide (CpG ODN) is recognized for its ability to activate cells to produce several cytokines, such as IL-12 and TNF-alpha. In the present study we have demonstrated that CpG ODN 1826, known for its immunostimulatory activity in the mouse system could, by itself, induce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production from mouse macrophage cell line (RAW 264.7). Neutralizing antibody against TNF-alpha was not able to inhibit NO or iNOS production from the CpG ODN 1826-activated macrophages, suggesting that although the TNF-alpha was also produced by CpG ODN-activated macrophages, the production of iNOS was not mediated through TNF-alpha. Although both CpG ODN 1826 and lipopolysaccharide (LPS) were able to stimulate NO and iNOS production, the exposure time required for maximum production of NO and iNOS for the CpG ODN 1826-activated macrophages was significantly longer than those activated with LPS. These results were due probably to a delay of NF-kappaB translocation, as indicated by the delay of IkappaBalpha degradation. Moreover, the fact that chloroquine abolished NO and iNOS production from the cells treated with CpG ODN 1826 but not from those treated with LPS suggested that the induction of NO and iNOS production from the cells stimulated with CpG ODN (1826) also required endosomal maturation/acidification. 相似文献