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)

To investigate the role of interleukin-1 (IL-1) in lipopolysaccharide (LPS)-induced sickness behavior, rats were injected with recombinant human interleukin-1 receptor antagonist (IL-1ra), an endogenous cytokine able to block most of the biological effects of IL-1 both in vivo and in vitro. Intraperitoneal injection of IL-1ra (3 mg/rat) attenuated the depressive effect of LPS (250 micrograms/kg) on social exploration and body weight when both treatments were injected peripherally. Intracerebroventricular injection of IL-1ra (60 micrograms/rat) did not block the effects of peripherally injected LPS. These data indicate that the peripherally mediated effects of IL-1 account for a significant part of LPS-induced sickness behavior.
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PMID:Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat. 138 28

The cDNA coding for xanthine dehydrogenase (XD) is isolated from mouse liver mRNA by cross-hybridization with a DNA fragment of the Drosophila melanogaster homologue. Two lambda bacteriophage overlapping clones represent the copy of a 4538-nucleotide-residue-long transcript with an open reading frame of 4005 nucleotide residues, coding for a putative polypeptide of 1335 amino acid residues. Comparison of the deduced amino acid sequence of the mouse XD with those of the Drosophila and the rat homologues shows a high conservation of this protein (55% identity between mouse and Drosophila, and 94% identity between mouse and rat). RNA blotting analysis demonstrates that interferon-alpha (IFN-alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver. Poly(I).poly(C) also induces XD mRNA in several other tissues in vivo. Protein synthesis de novo is not required for the elevation of XD mRNA after IFN-alpha treatment, since cycloheximide does not block the induction. The elevation of XD mRNA concentration is relatively fast and precedes the induction of both XD and xanthine oxidase (XO) enzymic activities.
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PMID:Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo. 159 Jul 74

Intravenous treatment of male rats with recombinant human interleukin-6 (rhIL6) at 50, 100 and 200 micrograms/kg (corresponding to 4, 8 and 16 x 10(4) U/animal, respectively) reduced the activities of hepatic microsomal cytochrome P450-dependent monoxygenases to varying degrees. Ethylmorphine-N-demethylase activity fell to 53% of control values, an effect similar to that induced by 2.5 mg/kg Escherichia coli lipopolysaccharide (LPS). Ethoxycoumarin-O-deethylase activity was also sensitive to inhibition, whereas IL6 had little effect on the activities of other P450-dependent enzymes, including ethoxyresorufin-O-deethylase. Pentoxyresorufin dealkylase activity, which is representative of the cytochrome P450 IIB 1/2 subfamily, was unaffected by IL6 whereas LPS reduced it to 33.7% of control values. Another hepatocyte-related parameter, serum concentration of alpha 1-acid glycoprotein (AGP), was increased by up to 3.5-fold over baseline by IL6 and 10-fold by LPS. Recombinant human interleukin-1 beta (rhIL1 beta) (10 micrograms/kg, corresponding to 5 x 10(4) U/rat) and recombinant human tumor necrosis factor alpha (rhTNF) (150 micrograms/kg corresponding to 24 x 10(4) U/rat) were both as potent as LPS (2.5 mg/kg) in increasing serum AGP levels and reducing hepatic microsomal monoxygenase activities. IL6 did not potentiate the effects of rhIL1 beta. Hepatic microsomal glucuronyltransferase activities were little affected by LPS and unaffected by rhIL6. Finally, rhIL6 was more potent after i.p. injection than after i.v. or s.c. injection. These results suggest that the effects of LPS, TNF and IL1 on the mixed-function oxidase system in vivo may be due partly to an induction of IL6 in vivo. The different sensitivities of the enzymes to IL6 but not to IL1 or TNF may be due to the involvement of two distinct mechanisms.
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PMID:Effects of interleukin-6 on cytochrome P450-dependent mixed-function oxidases in the rat. 163 28

We used male Wistar rats to determine the effects of lipopolysaccharide (LPS) on gastric secretion. After pylorus ligation, 24-h fasted rats received i.p. injections of different doses of LPS dissolved in sterile saline. The amounts of gastric acid and pepsin secreted were determined 2, 4 or 8 h after injection. Small doses of LPS (10-1000 ng/rat) significantly inhibited the release of both gastric secretants as compared with control animals, and this inhibitory effect of LPS on gastric secretion was dose-related. The gastric antisecretory effect of LPS was still evident 8 h after injection, indicating that this action of LPS was long-lasting. These results suggest that LPS might be involved in the regulation of gastric secretion under certain pathophysiological conditions such as acute bacterial infections.
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PMID:Lipopolysaccharide-induced inhibition of gastric acid and pepsin secretion in rats. 211 40

Intravenous (i.v. 320 and 640 micrograms/kg) and intracerebroventricular (i.c.v.; 1 microgram/rat) injection of Escherichia coli lipopolysaccharide (LPS) powerfully inhibited drinking induced by 24 h water deprivation. Pretreatment with acetylsalicylic acid (ASA) into the preoptic area (POA) completely abolished the effect induced by i.v. LPS, but did not modify that elicited by i.c.v. LPS. Intraperitoneal ASA injections significantly reduced the antidipsogenic effect of i.c.v. LPS. Electrolytic ablation of the subfornical organ (SFO) did not modify the effect induced by either i.v. or i.c.v. LPS. Present findings indicate that: (1) the antidipsogenic effect of i.v. LPS is mediated by prostaglandin synthesis into the POA, (2) the SFO is not involved in this effect, and (3) prostaglandins in other brain areas, besides POA, modulate the effect of i.c.v. LPS. It is suggested that at least two different brain sites, inside the blood-brain barrier, might be involved in the antidipsogenic effect of LPS.
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PMID:Endotoxin inhibition of drinking behaviour in the rat. 218 21

1. Key features of the acute phase response to infection are replicated by systemic administrations of lipopolysaccharide and may be mediated via the production of lymphokines and cytokines, including interleukin-1. Inhibition of prostaglandin synthesis may attenuate certain features of the acute phase response. 2. In the present study, the effects of systemic administration of the lipopolysaccharide (LPS, 250 micrograms/rat) and interleukin-1 (IL-1, 10 micrograms/rat) on catecholamine metabolism in different brain regions were compared and the effects of indomethacin, a cyclooxygenase inhibitor was determined. 3. The ratio of metabolite to parent amine was used as an index of turnover of catecholamines. 4. In hypothalamus, both epinephrine and norepinephrine concentrations were decreased and their major metabolite, 3-methoxy,4-hydroxyphenylglycol (MHPG), was elevated at 4, 8 and 24 hr following LPS. The major metabolite of dopamine (homovanillic acid, HVA) was increased at 8 hours in striatum, hypothalamus and medulla. LPS increased dopamine turnover at 8 and 24 hr and norepinephrine turnover at 4, 8 and 24 hr. 5. In all regions examined, IL-1 produced effects similar to LPS on amine and metabolite contents and norepinephrine and dopamine turnover. 6. Significantly, co-administration of a single dose of indomethacin (50 mg/kg) completely blocked LPS-induced changes in hypothalamic catecholamines and metabolites and the increase in turnover at 4 and 8 hr. Furthermore, the effects of IL-1 on hypothalamic MHPG content and norepinephrine turnover were also blocked by indomethacin, although the effects of IL-1 on regional catecholamines and HVA content and turnover were either not modified or partially antagonized by indomethacin. 7. The present results suggest that in the rat, activation of noradrenergic, dopaminergic and epinephrine-containing neurons in hypothalamus, as well as dopaminergic neurons in other regions is associated with the acute phase response to endotoxin and that synthesis of prostaglandins plays a pivotal role in catecholamine responses in all brain regions examined.
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PMID:Indomethacin prevents increased catecholamine turnover in rat brain following systemic endotoxin challenge. 223 87

We have previously produced an experimental model of ischemic bowel necrosis in the rat by injecting platelet activating factor (PAF) (7 micrograms/kg) into the mesenteric vascular bed. The dose of PAF required to produce necrosis could be reduced to 50% if the animal was pretreated with bacterial endotoxin (lipopolysaccharide) (20 micrograms/rat). The mechanism of this potentiating effect of lipopolysaccharide is unclear, but activation of the complement system may be one of the contributing factors. To investigate the role of the complement system, we injected cobra venom factor (CVF) (1 unit/kg) to activate the complement system before injection of PAF (2 micrograms/kg) into the superior mesenteric artery. CVF and PAF were also injected separately at the same dosage to other groups of rats. CVF activated the complement system, but by itself did not produce gross necrosis of the bowel. PAF alone caused 3 out of 9 rats treated to develop bowel necrosis. In contrast, combination of the two produced bowel necrosis in all 6 rats thus treated. CVF did not enhance the effects of PAF on hemoconcentration and leukopenia, but aggravated the hypotension caused by PAF. PAF, on the other hand, also enhanced activation of the complement system by CVF. To investigate the specificity of PAF on complement activation, lyso-PAF was used in combination with CVF. It was found that lyso-PAF did not have a significant potentiating effect on CVF-induced complement activation and, by itself, it had no effect on complement activation, blood pressure, white blood cell count or hematocrit. Lyso-PAF, with or without CVF, also failed to produce bowel necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cobra venom factor, an activator of the complement system, enhances the bowel necrosis induced by platelet-activating factor. 336 May 96

Uveitis can be induced by systemic or intravitreal administration of endotoxin (lipopolysaccharide, LPS). In this study we correlated the expression of class II antigens (la in rat) of the Major Histocompatibility Complex (MHC), with this experimental model of uveitis. Ia antigen was detected by immunohistochemistry using the Avidin-Biotin-Peroxidase Complex (ABC) method and the monoclonal antibody OX6. Ia antigen was not expressed in normal eyes. However, Ia was expressed in the anterior uvea epithelial cells in all eyes with LPS induced uveitis. This study demonstrates that the ocular Ia expression is a localized process in the anterior uvea in response to systemic or intravitreal LPS. This response appears to be distinct from the action of LPS on macrophage Ia expression, where LPS has been shown to inhibit the induction of Ia antigen in macrophages by gamma interferon.
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PMID:Expression of class II antigen in endotoxin induced uveitis. 353 20

Shigella sonnei lipopolysaccharide (LPS) was injected intravenous (iv) or into the lateral cerebral ventricle (icv) of freely moving rats. Iv injection of 320 micrograms/Kg reduced arterial blood pressure, increased heart rate and did not change pressor response and reflex bradycardia induced by iv bolus injection of phenylephrine (5 micrograms/Kg). Iv injection of 640 micrograms/Kg reduced arterial blood pressure and heart rate, and altered baroreceptor reflexes. Icv injection of LPS (up to 50 micrograms/rat) neither changed resting blood pressure and heart rate nor modified phenylephrine induced pressor response and reflex bradycardia. Results suggest that S. sonnei endotoxin determines cardiovascular changes mainly through baroreceptor resetting. Data also seem to rule out a central nervous system involvement.
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PMID:Cardiovascular responses of conscious rats to acute intravenous and intracerebroventricular administration of Shigella sonnei endotoxin. 636 36

Nitric oxide released in large amounts by inducible nitric oxide synthase (iNOS)-containing pulmonary cells plays an important role in many aspects of lung function in health and disease. The aim of this study was to establish a permanent non tumor-derived alveolar epithelial cell line that exhibits the typical characteristics of an iNOS-expressing cell. Therefore, the pulmonary epithelial cell line L2 (adult rat) was incubated with lipopolysaccharide derived from Escherichia coli (serotype 0111:B4) and different cytokines. The strongest effect on iNOS gene expression and nitric oxide release could be detected when L2 cells were coincubated with interferon-gamma + tumor necrosis factor-alpha. iNOS complementary DNA concentration was 25 amol/microliters at 9h, and nitrite/nitrate levels were 99.43 +/- 3.97 nmol/10(6) cells at 24h, respectively. Our results show that L2 cells can be regarded as an appropriate model for investigating iNOS gene expression and nitric oxide functions in alveolar epithelial cells.
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PMID:The pulmonary epithelial cell line L 2 as a new model for an inducible nitric oxide synthase expressing distal airway epithelial cell. 750 38


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