UNIPROT:P43026 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.
...
PMID:Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. 944 7

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.
...
PMID:Role of interleukin-10 in the lung response to silica in mice. 944 45

This study demonstrates that the therapeutic effect of a nitric oxide inhibitor in a murine model of fecal peritonitis is mediated in part by increased levels of interleukin-10 (IL-10) and monocyte chemoattractant protein 1 (MCP-1). Female CD1 mice were subjected to cecal ligation and puncture (CLP) with a 21-gauge needle and, immediately following surgery, were injected intraperitoneally with saline, N(G)-nitro-L-arginine methyl ester (L-NAME; 8 mg/kg), or N(G)-nitro-D-arginine methyl ester (D-NAME; 8 mg/kg). At 96 h after surgery and drug treatment, 20% of mice that received D-NAME had survived whereas 60% of mice that received L-NAME were alive. To elucidate the effect of L-NAME treatment on chemokine and cytokine production during fecal peritonitis, the levels of macrophage inflammatory protein 2 (MIP-2), IL-10, and MCP-1 were measured in peritoneal washings from additional groups of mice 24 h after the CLP surgery. Peritoneal fluids from L-NAME-treated mice contained significantly higher levels of IL-10 and MCP-1 than did those from D-NAME-treated mice. To elucidate the effect of nitric oxide inhibition on potential cellular sources of IL-10 and MCP-1 in the CLP model, cultured alveolar and peritoneal macrophages were activated with bacterial lipopolysaccharide in the presence of L-NAME; these macrophages produced significantly more MCP-1 than did similarly activated macrophages in the presence of D-NAME. In the CLP surgery model, immunoneutralization of IL-10 alone or IL-10 and MCP-1 together with polyclonal antibodies prior to surgery significantly reduced the survival rates in L-NAME-treated groups compared with L-NAME-treated groups that received preimmune serum. Taken together, these data demonstrate that the inhibition of nitric oxide following experimental CLP fecal peritonitis is therapeutic, in part through the modulatory effect of this treatment on the synthesis of IL-10 and MCP-1.
...
PMID:Therapeutic effects of nitric oxide inhibition during experimental fecal peritonitis: role of interleukin-10 and monocyte chemoattractant protein 1. 945 22

It was demonstrated that doxycycline protected BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) against lethal septic shock. Doxycycline (at 1.5 mg/kg) exerted its protective effect by inhibiting nitrate production by an interleukin-10-independent mechanism. Experiments carried out in vitro also indicated that doxycycline inhibited NO synthesis by LPS-activated macrophages without inducing any significant modification in interleukin-10 release. These data suggest that the direct inhibition of nitrate release is the main mechanism of the antiinflammatory activity of doxycycline in septic shock.
...
PMID:Doxycycline reduces mortality to lethal endotoxemia by reducing nitric oxide synthesis via an interleukin-10-independent mechanism. 946 45

Premature labor, fetal demise, and fetal growth restriction are accompanied by indices of inflammation or infection of the uteroplacental unit. To understand whether these events are causally related, we established an animal model of fetal demise and growth restriction and evaluated the potential utility of the anti-inflammatory cytokine interleukin-10 (IL-10). We administered low-dose endotoxin (lipopolysaccharide, or LPS, 100 microg/kg, i.p.) to third trimester rats (gestational days 14-20). Control rats received normal saline. A third group received IL-10 (100 microg/kg; s.c.) concomitantly with LPS for 7 prenatal days. Cytokine gene expression (IL-10 and TNF-alpha) was evaluated by RT-PCR and tissue levels (TNF-alpha) were determined by ELISA. Apoptosis was evaluated by TdT-mediated dUTP nick end labeling immunohistochemistry, and nitric oxide (NO) levels were quantified by microelectrode electrochemical detection in explants in culture media. LPS exposure resulted in 43% fetal demise and reduced the size of the surviving fetuses. Placental weight was not altered by LPS. IL-10 attenuated the LPS-induced fetal death rate (to 22%) and growth restriction (P<0.05). In normal rats, IL-10 did not affect fetus size or the incidence of resorptions, although placental size was marginally smaller. Increased uterine TNF-alpha content and NO release and apoptosis of uterine epithelia and muscularis were hallmarks of the LPS model. All were normalized by IL-10. IL-10 may represent a new therapeutic option for the treatment of a variety of perinatal complications. Benefit may result from the suppression of TNF-alpha- and NO-mediated cell death.
...
PMID:Interleukin-10 attenuates experimental fetal growth restriction and demise. 947 84

The level of intracellular cyclic nucleotides is a regulatory factor in a variety of immune processes. Increases in intracellular cyclic AMP (cAMP) and/or cyclic GMP (cGMP) concentration by the inhibition of phosphodiesterase have been shown to modulate the inflammatory response. Amrinone is a clinically used positive inotropic agent which elevates intracellular cAMP and cGMP levels by selective inhibition of the phosphodiesterase III isoenzyme. In the current study, we investigated the effect of various concentrations (1-300 microM) of amrinone on lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and of nitric oxide (NO) in vitro. In cultured murine J774.1 macrophages, 1 ng/ml-10 microg/ml of lipopolysaccharide from Escherichia coli O55:B5 induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and nitrite (breakdown product of NO). Pretreatment of cells with amrinone caused a dose-dependent suppression of TNF-alpha production in the concentration range of 1-100 microM. Furthermore, this drug suppressed NO production in the range of 30-300 microM. Similarly to the results in the J774.1 cells, amrinone also inhibited TNF-alpha and NO production in the range of 10-100 microM in primary rat peritoneal macrophages. At 300 microM, but not at lower concentrations, amrinone inhibited interleukin-10 production in lipopolysaccharide-treated J774.1 macrophages. Pretreatment of the macrophages with 100 and 300 microM amrinone increased the lipopolysaccharide-elicited translocation of nuclear factor-kappa B. Taken together, our results indicate that the phosphodiesterase III inhibitor amrinone modulates the activation/production of many pro- and anti-inflammatory factors in endotoxin-stimulated cells. It remains to be further investigated how such immunomodulatory effects contribute to the clinical profile of the agent.
...
PMID:Effect of the phosphodiesterase III inhibitor amrinone on cytokine and nitric oxide production in immunostimulated J774.1 macrophages. 947 38

Agmatine is an amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC) and metabolized to putrescine by agmatinase. While prevalent in bacteria and plants, agmatine and its metabolic enzymes have been recently identified in mammalian tissues. In the present study we sought to determine: (a) whether macrophages (cell line RAW 264.7) express ADC and agmatinase, and (b) if the enzymes are regulated by lipopolysaccharide (LPS), and/or by the inhibitory cytokines transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10) and interleukin-4 (IL-4). LPS induced a dose-dependent stimulation of agmatinase, while it decreased ADC, the effect in both cases being maximum at 20 h. As expected, LPS dose-dependently stimulated the inducible nitric oxide synthase activity (iNOS). A strong correlation was observed between the effects of LPS on the agmatine-related enzymes and iNOS. By contrast, exposure to IL-10 and TGF-beta caused a reduction in ADC and agmatinase, whereas IL-4 was ineffective on ADC, but reverted the LPS-induced increase of agmatinase. We conclude that the agmatine pathway may be an alternative metabolic route for arginine in macrophages, suggesting a regulatory role of agmatine during inflammation.
...
PMID:Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines. 949 13

We examined the pathogenesis of the facultative intracellular bacterium, Salmonella typhimurium in MHCII-/-, C2D knock-out mice, and wild-type C57BL/6J mice. The MHCII knock-out shortened the kinetics of animal death and reduced the dose of S. typhimurium needed to kill mice. We measured the physiological and cytokine responses of both mouse strains after S. typhimurium injection. Animal weight loss, spleen weights, liver weights, thymus weights, and serum corticosterone concentrations were comparable after injection with several doses of bacteria. The only physiological differences observed between the two strains were observed 3 days after injection of the highest dose of bacteria tested. Serum concentrations of tumor necrosis factor alpha, interleukin-2, and interleukin-6 increased in a dose-dependent fashion irrespective of mouse MHCII expression. Therefore, even in the absence of MHCII, mice are able to mount relatively normal physiological and immunological responses. Consistent with these normal responses, an increased percentage of MHCII-/- mice, primed with a low dose of bacteria 13 days earlier, were able to survive a lethal challenge of Salmonella compared with unprimed controls. Lastly, C2D mice had significantly higher serum interleukin-10 concentrations than C57BL/6J mice 48 h after infection with all doses of S. typhimurium. C2D macrophages also secreted significantly more IL-10 and less NO and O2- after lipopolysaccharide or phorbol ester stimulation in vitro than wild-type macrophages.
...
PMID:Salmonella infections in the absence of the major histocompatibility complex II. 950 May 16

The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS tolerance or endotoxin desensitization. LPS tolerance, which can be experimentally induced in vitro and in vivo, is also known to occur in septic disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen-presenting cells, are also subject to this phenomenon. Single doses of LPS added at the initiation of DC culture inhibited in a dose-dependent fashion the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and IL-12, but not the production of IL-8, in response to a second LPS challenge in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation antigen was inhibited in these cells. Moreover, the endocytic activity of DC generated in the presence of LPS was dramatically reduced. DC desensitized with LPS were potent stimulators of T-cell proliferation but poor inducers of interferon-gamma (IFN-gamma) production in the allogeneic mixed leukocyte reaction. TNF-alpha and prostaglandin E2, two major products of LPS stimulation, could replace LPS for the induction of tolerance to LPS. Moreover, treatment of desensitized DC with TNF-alpha plus prostaglandin E2 fully restored CD83 expression and partially restored IL-12 production as well as the IFN-gamma-inducing activity of DC in the mixed leukocyte reaction. Our data show that human DC are highly susceptible to the induction of LPS tolerance, which seems to be a state of differential deactivation in which some functions are impaired whereas others are retained. Tolerization at the level of the professional antigen-presenting cell by inflammatory mediators may play an important role in septic disease and in the origin of cancers associated with chronic inflammation.
...
PMID:Differential deactivation of human dendritic cells by endotoxin desensitization: role of tumor necrosis factor-alpha and prostaglandin E2. 955 64

Antigen-presenting cells are thought to modulate the development of Th1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12. Because glucocorticoids (GC) favor the development of Th2 responses, we determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12 production in whole-blood cultures. Significant inhibition of IL-12(p40) and IL-12(p70) was found with 10(-8) mol/L and 10(-9) mol/L DEX respectively, whereas IL-10 was relatively insensitive or even stimulated. Accordingly, the expression of IL-12(p40) and IL-12(p35) mRNA was more sensitive to DEX than IL-10 mRNA. The glucocorticoid receptor (GR) antagonist RU486 enhanced IL-12 production and largely abrogated the inhibition of IL-12 by GC, indicating that this suppression was mainly GR-mediated. High concentrations of RU486 were inhibitory for IL-10, suggesting that GC may exert a positive effect on IL-10. In the presence of neutralizing anti-IL-10 antibodies, DEX was still capable of IL-12 suppression whereas RU486 still enhanced IL-12 production, indicating that GC do not modulate IL-12 via IL-10 exclusively. Taken together these results indicate that GC may favor Th2 development by differential regulation of IL-10 and IL-12.
...
PMID:Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro. 959 74

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>