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)

Zinc is an essential heavy metal for the normal function of the central nervous system (CNS), but the knowledge of its metabolism and functions is scarce. In this report we have studied the effect of a zinc deficient diet on the regulation of brain metallothioneins (MTs). In situ hybridization analysis revealed that brain MT-I induction by restraint stress was significantly blunted in some but not all brain areas in the mice fed the zinc deficient diet compared to normally fed mice. In contrast, brain MT-I induction by the administration of bacterial lipopolysaccharide (LPS) was not significantly lower in the mice fed the zinc deficient diet. In contrast to MT-I, MT-III mRNA levels were minimally affected by either stress or LPS. Yet, significant decreasing effects of the zinc deficient diet were observed in areas such as the neocortex, CA1-CA3 neuronal layer and dentate gyrus of the hippocampus, and the Purkinje neuronal layer of the cerebellum. These results demonstrate that dietary zinc deficiency impairs the response of brain MTs during both stress and LPS-elicited inflammatory response in a highly specific manner.
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PMID:Effect of dietary zinc deficiency on brain metallothionein-I and -III mRNA levels during stress and inflammation. 1076 93

The influence of CdCl(2), used at 1, 10 and 100 microM concentration, and ZnCl(2) at 1, 10 and 100 microM concentration on the production of interferon (IFN) and tumor necrosis factor (TNF) in bovine aorta endothelial cells (BAECs) was examined. BAECs were treated with cadmium ions or zinc ions alone or together with cytokine inducers: Newcastle disease virus (NDV) and lipopolysaccharide (LPS). Cadmium ions at 1 and 10 microM concentration, used alone induced a low, but detectable TNF activity in BAECs, and zinc ions at 1, 10 and 100 microM concentration induced both IFN and TNF activity. In contrast to that, cadmium added to BAECs together with the virus or LPS as cytokine inducers significantly inhibited the production of IFN and TNF. Cadmium effect depended on the concentration used, and 1 and 10 microM CdCl(2) partially, but 100 microM cadmium completely inhibited the production of both cytokines. Zinc ions at 1 and 10 microM concentration, which only slightly inhibited the production of both cytokines, did not reconstitute cadmium-depressed IFN and TNF production. These data indicate that cadmium-induced depression of cytokine production in bovine endothelial cells, in response to viral and bacterial stimuli, cannot be reversed by zinc supplementation.
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PMID:The influence of cadmium and zinc ions on the interferon and tumor necrosis factor production in bovine aorta endothelial cells. 1077 Nov 38

Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin, iron, and CO. The inducible isoform (HO-1) has been implicated as a modulator of the inflammatory response. HO-1 activity can be induced by hemin and inhibited with zinc protoporphyrin IX (ZnPP). Using these reagents, we assessed the possibility that HO-1 modulates the inflammatory response by altering the expression of endothelial cell adhesion molecules. Endotoxin (lipopolysaccharide, LPS)-induced expression of P- and E-selectin expression was quantified in different vascular beds of the rat using the dual radiolabeled monoclonal antibody technique. Pretreatment with hemin attenuated, whereas ZnPP treatment exacerbated, the increased selectin expression normally elicited by LPS. Biliverdin, at an equimolar dosage, was as effective as hemin in attenuating LPS-induced selectin expression in the lung, kidneys, liver, and intestines. These findings indicate that the anti-inflammatory properties of HO-1 may be related to an inhibitory action of P- and E-selectin expression in the vasculature. Biliverdin (or its metabolite, bilirubin), rather than CO, may account for this action of HO-1 on endothelial cell adhesion molecule expression.
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PMID:Heme oxygenase modulates selectin expression in different regional vascular beds. 1077 41

1. The ulcerogenesis of gastric haemorrhagic damage during sepsis is unclear. The present study first proposes that gastric haemorrhagic ulcer is modulated by mucosal glutathione, histamine and oxyradicals in lipopolysaccharide (LPS)-induced sepsis in rats. The protective effects of several drugs on the ulcerogenic parameters also were evaluated. 2. Male specific pyrogen-free Wistar rats were deprived of food for 24 h. For the induction of sepsis, intravenous LPS (0, 1, 3 or 10 mg/kg in 1 mL sterilized normal saline) was challenged to rats 12 h after withdrawal of food. Rat stomachs were vagotomized, followed by irrigation for 3 h with normal saline or a physiological acid solution containing 100 mmol/L HCI and 54 mmol/L NaCl. 3. The aggravation of gastric ulcerogenic parameters, such as gastric acid back-diffusion, luminal haemoglobin content, mucosal lipid peroxide production, histamine concentration, as well as lowered concentrations of defensive substances, including mucosal glutathione, were dependent on the doses of LPS used for challenge. A high correlation was observed between mucosal histamine release and lipid peroxide production in LPS rats. 4. The ulcerogenic parameters obtained in LPS (3 mg/kg, i.v.) rats were potently attenuated by diamine oxidase, ketotifen and zinc sulphate. 5. Several oxyradical scavengers, including glutathione, dimethylsulphoxide and allopurinol, also were effective in inhibiting haemorrhagic ulcer. 6. In conclusion, gastric mucosal histamine release and oxyradical generation play pivotal roles in the formation of haemorrhagic ulcers in septic rats.
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PMID:Importance of histamine, glutathione and oxyradicals in modulating gastric haemorrhagic ulcer in septic rats. 1077 30

1. Haem oxygenase-1 (HO-1) can exert protective effects against oxidative stress and inflammation. Fibroblasts participate in inflammatory responses where they produce high levels of prostaglandins (PGs) and nitric oxide (NO). However, little is known of the presence of HO-1 in these cells and the possible interactions among these pathways. Incubation of cells with NO donors, spermine nonoate (SPNO) and S-nitroso-N-acetylpenicillamine (SNAP), induced a dose- and time-dependent expression of HO-1 protein. 2. NO donors increased basal PGE(2) release although they reduced PGE(2) accumulated in the medium and cyclo-oxygenase (COX) activity when cells were stimulated with lipopolysaccharide (LPS). COX-2 protein was weakly induced by SPNO in basal conditions and in the presence of LPS a synergy for HO-1 and COX-2 protein expression was observed. 3. Our results indicate that reactive oxygen species participate in the inductive effect of NO donors or LPS on HO-1 expression, whereas endogenous NO production may play a role in the mechanism of the synergy exhibited by SPNO and LPS on HO-1 and COX-2 expression. In this system, zinc protoporphyrin IX did not affect nitrite levels but reduced COX activity. 4. The selective COX-2 inhibitors SC58125 and NS398 as well as the non-selective COX inhibitor, indomethacin, strongly reduced PGE(2) synthesis and showed a synergy with NO donors in HO-1 and COX-2 induction. Addition of PGE(2) had no effect, suggesting a mechanism independent of PGs formation. 5. In inflammatory conditions a number of factors could cooperate to induce HO-1 and COX-2, with a positive regulation by COX inhibitors.
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PMID:Enhanced expression of haem oxygenase-1 by nitric oxide and antiinflammatory drugs in NIH 3T3 fibroblasts. 1078 Sep 98

Cysteine-rich intestinal protein (CRIP), a member of the LIM protein family, has a unique double zinc finger motif as the defining feature. CRIP is highly expressed in intestine and immune cells. CRIP transgenic (Tg) mice and nontransgenic controls were challenged with lipopolysaccharide (LPS). Serum concentrations of interferon-gamma and tumor necrosis factor-alpha were less while those of interleukin-6 and -10 were greater in the Tg mice following LPS administration. CRIP-overexpressing splenocytes produce the same cytokine profile. These responses are consistent with a regulatory role for this protein in cell differentiation, which produces an imbalance in Th1 and Th2 cytokines. Stimulation of CRIP protein levels by LPS is eliminated in metallothionein knockout mice, suggesting metallothionein is the source of zinc for this zinc finger protein and, further, that this could reflect a relationship to the zinc nutritional status and to the aberrant Th1/Th2 cytokine balance observed in zinc deficiency.
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PMID:Regulation of cysteine-rich intestinal protein, a zinc finger protein, by mediators of the immune response. 1094 88

Immune function is markedly attenuated in endotoxemia. Zinc is involved in the regulation of cellular functions and maintenance of immune function, and its level in the serum is low in endotoxemia. We mainly investigated the effects of zinc acetate (ZA) on splenocytes in mice with endotoxemia. After we confirmed increased plasma zinc level by ZA treatment, C57BL/6 mice were randomly divided into four groups: 10 control mice received 500 microL saline solution as vehicle; 10 control mice received ZA at 3 mg/kg body weight; 20 endotoxemic mice received a 40 mg/kg lethal dose of lipopolysaccharide (LPS); 20 mice received ZA followed by LPS as the above dose. In vivo, we confirmed that ZA pretreatment did not significantly affect the plasma cytokine level in endotoxemic mice. In vitro, splenocytes from ZA-plus-LPS mice showed drastic effects, in that ZA abrogated LPS-induced suppression of cellular proliferation and production of interleukin-2 and interferon-gamma. The percentage of apoptotic splenocytes was significantly reduced in ZA-plus-LPS mice (23.4%) as compared with LPS mice (41.6%). Furthermore, the expression of HSP-70 mRNA in splenocytes was strongly enhanced in both ZA and ZA-plus-LPS mice, especially in the latter group. Finally, studies monitoring survival rates for 6 days showed that LPS caused 100% mortality while ZA-plus-LPS mice showed 75% survival. Our results suggest that zinc normalized the immune response and reduced apoptosis of splenocytes. These changes were probably caused by increased synthesis of HSP-70 by splenocytes, which might enhance survival of mice with LPS-induced endotoxemia.
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PMID:Effects of zinc acetate on splenocytes of endotoxemic mice: enhanced immune response, reduced apoptosis, and increased expression of heat shock protein 70. 1115 21

We have recently reported that the central heme oxygenase (HO) pathway has an important role in the genesis of lipopolysaccharide fever. However, the HO product involved, i.e., biliverdine, free iron, or carbon monoxide (CO), has not yet been identified with certainty. Therefore, in the present study, we tested the thermoregulatory effects of all HO products. Body core temperature (T(c)) and gross activity of awake, freely moving rats was measured by biotelemetry. Intracerebroventricular administration of heme-lysinate (152 nmol), which induces the HO pathway, evoked a marked increase in T(c), a response that was attenuated by intracerebroventricular pretreatment with the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (200 nmol), indicating that an HO product has a pyretic action in the central nervous system (CNS) of rats. Besides, heme-lysinate also increased gross activity, but no correlation was found between this effect and the increase in T(c). Moreover, intracerebroventricular biliverdine or iron salts at 152 nmol, a dose at which heme-lysinate was effective in increasing T(c), produced no change in T(c). Accordingly, intracerebroventricular treatment with the iron chelator deferoxamine elicited no change in basal T(c) and did not affect heme-induced pyresis. However, heme-induced pyresis was completely prevented by the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one. Because biliverdine and iron had no thermoregulatory effects and CO produces most of its actions via sGC, these data strongly imply that CO is the only HO product with a pyretic action in the CNS.
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PMID:Carbon monoxide is the heme oxygenase product with a pyretic action: evidence for a cGMP signaling pathway. 1120 74

The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.
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PMID:Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. 1122 21

Experiments were conducted to determine the effect of injection of lipopolysaccharide (LPS, from S. typhimurium) or muramyl dipeptide (MDP, N-acetylmuramyl-L-ala-isoglutamine) in Japanese quail. Doses of MDP between 0.3 and 10 mg/kg body wt. had no effect on body temperature. In contrast, doses of 1.0-22.5 mg LPS/kg body wt. caused significant increases in body temperature. None of the doses of LPS or MDP resulted in mortality. The febrile response to LPS was diminished following a second injection 48 h after the first, and was absent following a third injection. Plasma zinc, an indicator of the acute phase response, was significantly reduced by either LPS or MDP after the first injection (P<0.001), but not after the second or third injection. Splenic interleukin 1-beta (IL-1beta) mRNA expression was increased after the first and last injection of LPS (P<0.001), but only after the first injection of MDP (P<0.005). Hepatic IL-1beta mRNA expression was increased after the first, but not the third injection of LPS (P<0.001), while MDP had no effect. These data indicate that Japanese quail are less sensitive to MDP than LPS, and that quail demonstrate tolerance to LPS following repeated injections.
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PMID:The acute phase response in Japanese quail (Coturnix coturnix japonica). 1123 38


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