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)

Spermine NONOate (SpNO, a nitric oxide donor) induced apoptosis and caspase-3 activity in the macrophage cell line RAW 267.4. RES cells that have been derived from RAW 267.4 cells by repeated exposure to lipopolysaccharide and interferon-gamma (LPS/INF-gamma), followed by outgrowth of viable cells, are resistant to apoptosis and caspase-3 activation upon exposure to SpNO. In this study we have determined that RES cells have lower levels of glutathione (GSH) and a higher oxidative state than RAW cells. Subsequently, RAW and RES cells were depleted of GSH by using l-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis. GSH depleted cells did not undergo apoptosis nor demonstrate caspase-3 activity when they were exposed to SpNO. These results suggest that the redox status of the cell is one of the key factors mediating the apoptotic pathway in which glutathione plays a critical role in mediating apoptosis via NO* and reactive oxygen species (ROS).
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PMID:Glutathione levels determine apoptosis in macrophages. 964 8

In the present study we evaluated the effects of NO synthase (NOS) induction on the regulation of cytochrome c oxidase (CO) and F0F1-ATPase subunit expression in astroglial and mixed cortical cell cultures. In mixed cortical cell cultures, 18 h of treatment with lipopolysaccharide (LPS, 0.1 microgram/mL) plus interferon-gamma (INF-gamma, 10 U/mL) caused an increase of mRNAs for CO-I, F0F1-ATPase 6 and also for iNOS at 20 DIV. The induction of both CO-I and F0F1-ATPase 6 was abolished by the NOS inhibitor N-monomethyl-L-arginine (NMMA) or by the enzymatic scavenger superoxide dismutase/catalase (SOD/CAT). In primary astroglial cell cultures, treatment for 18 h with increasing concentrations of LPS and INF gamma, produced an increase in the amount of mitochondrial encoded CO-I and -II subunits, with no significant modifications of nuclear encoded subunit IV. An increase was also observed at level of transcription for CO-I and -II, and F0F1-ATPase 6 mRNAs. These effects were abolished by addition of NMMA or SOD/CAT. mRNA induction of CO-I was higher in mixed cortical than in astroglial cell cultures while that of F0F1-ATPase 6 was similar in both cell types. These results suggest that the expression of mitochondrial encoded subunits (CO-I, CO-II and F0F1-ATPase 6) is up-regulated in response to oxygen and NO reactive species. The activity of cytochrome c oxidase decreased after LPS/INF gamma treatment in both astroglial and mixed cortical cultures. The activity of ATP synthase was unmodified, while ATP content drastically decreased after LPS/INF gamma treatment, in both astroglial and mixed cortical cultures. The enzymatic activities of catalase and Mn-SOD (mitochondrial) showed a significant increase after LPS/INF gamma treatment, which was abolished by NMMA.
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PMID:Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain enzyme subunits in mixed cortical and astroglial cell cultures. 989 46

When macrophages derived from rat bone marrow were cultured in the presence of polyanions such as acetyl lignin (EP3), sulfonyl lignin (LS) or dextran sulfate (DS), the cells secreted TNF-alpha, IL-8 and nitric oxide (NO). EP3 had a dose-dependent effect on the secretion of TNF-alpha, IL-8 and NO. EP3 significantly affected secretion at concentrations greater than 5 microg/ml. The EP3 effect was at its maximum between concentrations of 50 and 100 microg/ml. LS and DS induced a slight increase in the secretion of cytokines and NO at a concentration of 100 microg/ml. The use of the reverse-transcription polymerase chain reaction (RT-PCR) showed that the increases in cytokine and NO secretion were due to an increase in cytokine mRNAs or NO synthase mRNA. Anti-TNF-alpha antibodies partially inhibited NO secretion by EP3-activated macrophages, although IL-8 secretion was independent of antibody treatment. The secretion of TNF-alpha and NO was also unaffected by the addition of anti-IL-8 antibodies. The addition of interferon-gamma (IFN-gamma) to the culture medium did not alter TNF-alpha and NO secretion by the EP3-activated macrophages, however, IL-8 secretion was increased when a low concentration of IFN-gamma (0.2 U/ml) was added, but was reduced in the presence of a high concentration of IFN-gamma (2000 U/ml). IFN-gamma produced similar effects on cytokine and NO secretion in macrophages activated with lipopolysaccharide (LPS). Therefore, it is concluded that macrophages treated with polyanions secrete cytokines and NO, and that INF-gamma is involved in the regulatory mechanism of cytokine and NO secretion.
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PMID:Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with polyanions, and involvement of interferon-gamma in the regulation of cytokine secretion. 1043 3

The ergopeptine alkaloid ergotamine (ET) mimics the effects of ergopeptine alkaloids found in endophyte-infected (E+) fescue forage considered causative for fescue toxicosis. Altered immune capacity, compromised intake and thermoregulation, and inflammatory changes are observed in fescue toxicosis. Taken together, these suggest the cytokine pattern may be altered by ergot alkaloids. Thus, the objective of this study was to determine whether major splenocyte-derived cytokines--interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-gamma)--and macrophage-derived cytokines--interleukin 1beta, (IL-1beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)--were affected by ergotamine. Two sets of male BALB/c mice (n = 5/treatment) were treated with ergotamine tartrate (s.c.) for 10 d at doses of 0 (control), 0.4, 2, 10, or 50 mg/kg body weight. Twenty-four hours after the last treatment, splenocytes (S) were isolated from one set of animals and macrophages (Mphi) from the other set for determination of IL-2, IL-4, INF-gamma, and IL-1beta, IL-6, TNF-alpha, respectively. Following activation with 5 microg/ml concanavalin A (Con A) (S) and 10 microg/ml lipopolysaccharide (LPS) (Mphi), cells were incubated for 48 and 24 h, respectively, and supernatants were collected and assayed for respective cytokines by enzyme-linked immunosorbent assay (ELISA). Additionally, differential white blood cell (WBC) counts were performed and the neutrophil (N):lymphocyte (L) ratio calculated. Ergotamine treatment significantly increased IL-6 levels at the 2.0 mg/kg dose and greater and TNF-alpha at the highest dose. There was no treatment effect on IL-1beta, IL-2, IL-4, and IFN-gamma. Also, no effect was observed upon total and differential WBC counts as well as N:L ratio. Ergotamine affected the proinflammatory cytokine IL-6, and this increase may contribute to fescue tosicosis.
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PMID:Increased proinflammatory cytokines production by ergotamine in male BALB/c mice. 1052 46

Previous studies have suggested that cytokine production may play a role in the cerebral demyelination and phenotypical variations of X-linked adrenoleukodystrophy (ALD). At initial evaluation, the serum titre of tumour necrosis factor alpha (TNFalpha) but not interleukin IL-1alpha, IL-1beta, IL-6, IL-4 and interferon INF-gamma of 12 ALD patients with cerebral demyelination, was higher than that of controls and of six ALD patients without cerebral demyelination. However, TNFalpha was not detected in the cerebrospinal fluid of the same patients with cerebral demyelination. In a serial study of 15 patients over 2-5 years, the level of serum TNFalpha paralleled the progression of demyelination. Peripheral blood mononuclear cells from 15 symptomatic ALD patients, irrespective of their clinical phenotype, produced higher levels of TNFalpha than controls after in vitro stimulation by lipopolysaccharide. The production of other cytokines was normal. Abnormal production of TNFalpha was observed in two of six asymptomatic ALD patients but was absent in both of two bone marrow transplanted ALD patients. These data suggest that monocytes of ALD patients have an intrinsic alteration in the regulatory pathway of TNFalpha production.
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PMID:Excessive production of tumour necrosis factor alpha by peripheral blood mononuclear cells in X-linked adrenoleukodystrophy. 1072 43

Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOS-II) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-gamma and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-gamma alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis.
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PMID:Nitric oxide synthase type-II is synthesized by human gingival tissue and cultured human gingival fibroblasts. 1098 79

Although several studies have demonstrated that the pulmonary collectins surfactant protein (SP)-A and SP-D contribute to innate immunity by enhancing pathogen phagocytosis, the role of SP-A and SP-D in regulating production of free radicals and cytokines is controversial. We hypothesized that the state and mechanism of activation of the immune cell influence its response to SP-A. The effects of SP-A and SP-D on production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were assessed in isolated rat alveolar macrophages activated with lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or both agonists. SP-A inhibited production of NO and iNOS in macrophages stimulated with smooth LPS, which did not significantly bind SP-A, or rough LPS, which avidly bound SP-A. In contrast, SP-A enhanced production of NO and iNOS in cells stimulated with IFN-gamma or INF-gamma plus LPS. Neither SP-A nor SP-D affected baseline NO production, and SP-D did not significantly affect production of NO in cells stimulated with either LPS or IFN-gamma. These results suggest that SP-A contributes to the lung inflammatory response by exerting differential effects on the responses of immune cells, depending on their state and mechanism of activation.
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PMID:Surfactant protein A differentially regulates IFN-gamma- and LPS-induced nitrite production by rat alveolar macrophages. 1110 30

The effect of high-molecular-weight hyaluronan (HA) on peritoneal and systemic inflammation and peritoneal permeability to water and solutes was studied during endotoxin-induced peritonitis in rats. Acute peritonitis was induced by adding lipopolysaccharide (LPS) to the dialysis fluid (Dianeal 3.86; Baxter Healthcare, Ireland, Castlebar). HA was added to the dialysis solution in a concentration of 10 mg/dL. During 4- and 8-hour dwells of the dialysis fluid, we studied the intensity of peritoneal (dialysate) and systemic (blood) inflammation (dialysate cell count and differential, cytokine and HA levels), as well as the transperitoneal transport of solutes and water. In rats, the addition of LPS to the dialysis fluid induced changes in inflammatory reaction and transperitoneal transport similar to those seen in continuous ambulatory peritoneal dialysis patients with peritonitis. During peritonitis, the addition of HA to the dialysis fluid reduced the loss of ultrafiltration, which resulted in a greater peritoneal creatinine clearance during the 8 hours of dwell (29.9 +/- 6.7 mL/8 h in the HA-LPS group versus 19.7 +/- 7.8 mL/8 h in the LPS group; P < 0.05). Dialysate interferon-gamma (INF-gamma) levels during peritonitis were greater in HA-treated animals (536.8 +/- 296.6 pg/mL in the HA-LPS group versus 169.8 +/- 137.8 pg/mL in the LPS group; P < 0.05). Dialysate elastase activity increased during peritonitis (44.4 +/- 9.3 versus 14.2 +/- 4.1 U/mL in peritonitis-free rats); during peritonitis, the increase in dialysate elastase activity was less pronounced in the rats that had HA in the dialysate (27.3 +/- 4.1 U/mL versus the LPS group; P: < 0.01). We conclude that HA added to the dialysis fluid reduces loss of ultrafiltration during peritonitis in rats. In the presence of HA dialysate, INF-gamma levels during peritonitis increased, whereas elastase activity decreased; these changes might improve the peritoneal immune reaction during peritonitis and at the same time prevent peritoneal membrane injury.
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PMID:Hyaluronan modifies inflammatory response and peritoneal permeability during peritonitis in rats. 1122 85

Gap junctional communication between microglia was investigated at rat brain stab wounds and in primary cultures of rat and mouse cells. Under resting conditions, rat microglia (FITC-isolectin-B4-reactive cells) were sparsely distributed in the neocortex, and most (95%) were not immunoreactive for Cx43, a gap junction protein subunit. At brain stab wounds, microglia progressively accumulated over several days and formed aggregates that frequently showed Cx43 immunoreactivity at interfaces between cells. In primary culture, microglia showed low levels of Cx43 determined by Western blotting, diffuse intracellular Cx43 immunoreactivity, and a low incidence of dye coupling. Treatment with the immunostimulant bacterial lipopolysaccharide (LPS) or the cytokines interferon-gamma (INF-gamma) or tumor necrosis factor-alpha (TNF-alpha) one at a time did not increase the incidence of dye coupling. However, microglia treated with INF-gamma plus LPS showed a dramatic increase in dye coupling that was prevented by coapplication of an anti-TNF-alpha antibody, suggesting the release and autocrine action of TNF-alpha. Treatment with INF-gamma plus TNF-alpha also greatly increased the incidence of dye coupling and the Cx43 levels with translocation of Cx43 to cell-cell contacts. The cytokine-induced dye coupling was reversibly inhibited by 18 alpha-glycyrrhetinic acid, a gap junction blocker. Cultured mouse microglia also expressed Cx43 and developed dye coupling upon treatment with cytokines, but microglia from homozygous Cx43-deficient mice did not develop significant dye coupling after treatment with either INF-gamma plus LPS or INF-gamma plus TNF-alpha. This report demonstrates that microglia can communicate with each other through gap junctions that are induced by inflammatory cytokines, a process that may be important in the elaboration of the inflammatory response.
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PMID:Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. 1125 46

Transcript expression of 24 chemokines (CKs) was examined throughout 8 days in mouse lungs with type-1 (Th1) or type-2 (Th2) cytokine-mediated granulomas induced by bead-immobilized mycobacterial purified protein derivative or Schistosoma mansoni egg antigens. Where possible, CK protein levels were also measured. In addition, we examined effects of in vivo cytokine depletions. Findings were as follows: 1) bead challenge induced increases in 18 of 24 CK transcripts with type-1 and type-2 responses displaying different patterns. CKs fell into four categories: a) type-1-dominant (gamma-interferon-inducible protein (IP-10), monokine induced by INF-gamma (MIG), macrophage inflammatory protein-2 (MIP-2), lipopolysaccharide-induced chemokine (LIX), rodent growth-related oncogene homologue (KP), macrophage inflammatory protein-1alpha (MIP-1alpha) and -1beta (MIP-1beta), lymphotactin), b) type-2-dominant (eotaxin, monocyte chemotactic protein-2 (MCP-2) and -3 (MCP-3), liver and activation-regulated chemokine (LARC), T cell activation protein-3 (TCA-3), c) type-1 and type-2 co-dominant (MCP-1, MCP-5, monocyte-derived chemokine (MDC), thymus and activation-related chemokine (TARC), C10), and d) constitutive (lungkine, secondary lymphoid-tissue chemokine (SLC), EBI1-ligand chemokine (ELC), fractalkine, macrophage inflammatory protein-1gamma (MIP1-gamma), and stromal cell derived factor-1alpha (SDF1-alpha). 2) CKs displayed characteristic temporal patterns. CXC (IP-10, MIG, MIP-2, LIX, KC) and certain CC (MCP-1, MCP-5, MIP-1alpha, MIP-1beta) CKs were produced maximally within 1 to 2 days. Others (MCP-2, MCP-3, eotaxin, lymphotactin, LARC, TCA-3) displayed peak expression later. 3) Interferon-gamma neutralization profoundly abrogated MIG, but had little effect on other CKs. Tumor necrosis factor-alpha neutralization caused up to 50% reduction in a range of CKs. These findings indicate that type-1 and type-2 granulomas display characteristic CK profiles with coordinated expression that is under cytokine-mediated regulation.
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PMID:Chemokine expression dynamics in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation. 1129 May 68


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