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)

Consistent with stimulation of expression of an inducible form of nitric oxide synthase (iNOS), exposure of rat astroglial cultures to lipopolysaccharide (LPS) caused a time-dependent increase in the accumulation of nitrite in the culture media. Addition of the peptide angiotensin II (ANG II) with LPS decreased subsequent formation of nitrite in a concentration-dependent manner (concentration inhibiting 50% of maximal response approximately 1 nM). The ANG II effect could be blocked by the ANG II type 1 (AT1 receptor antagonist losartan but not by the ANG II type 2 (AT2) receptor antagonist PD-123177. ANG II had no effect on nitrite formation stimulated by a combination of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma). A brief 10-min exposure to ANG II was sufficient to cause an approximately 30% inhibition of the LPS response, with maximal inhibition of approximately 65% after 3 h, and occurred only when ANG II was added during the iNOS induction phase. Consistent with partial inhibition of LPS-stimulated expression of iNOS, ANG II reduced the levels of both iNOS mRNA and iNOS protein. These results demonstrate that ANG II can decrease LPS-stimulated NO production in astroglia by inhibiting induction of iNOS expression.
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PMID:Angiotensin II decreases inducible nitric oxide synthase expression in rat astroglial cultures. 753 84

The contraction elicited by angiotensin II (ANG II) was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 1 or 10 micrograms/ml Escherichia coli lipopolysaccharide endotoxin (LPS). This contraction was 18 and 71% greater for the two doses of LPS, respectively, than in unexposed control rings. In endothelium-denuded rings, the LPS-induced increase in contraction in response to ANG II was completely abolished. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that LPS interferes with this modulation. We found that the LPS-induced increase in contraction to ANG II was inhibited in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) or the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 (2 x 10(-7) M). Conversely, the LPS-induced increase in contraction in response to ANG II was not inhibited by the presence of dexamethasone (10(-6) M), which inhibits new protein synthesis. In addition, there was no loss of vasodilator response to the endothelium-dependent receptor agonist acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to norepinephrine (10(-9)-10(-5) M) and KCl (20-100 mM). We conclude that short exposure to LPS produces a specific increase in the constrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This effect could be a LPS-induced shift in favor of constrictor prostanoids in the balance of dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.
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PMID:Short exposure to endotoxin increases the constriction induced by angiotensin II in rat aorta. 884 78

In sepsis, lipopolysaccharide (LPS) depresses cardiac function by inducing production of nitric oxide (NO) and its second messenger cGMP. LPS also stimulates ANG II production. We hypothesized that ANG II modulates the cardiac response to LPS. Adult rabbit cardiac myocytes incubated with LPS (10 ng/ml) had increased cardiac cGMP after 6 h (but not within 1 h) [527 +/- 43 vs. 316 +/- 27 (SE) fmol/mg protein in controls, n = 16 each group, P < 0.05]. This was associated with depressed cell shortening with no alterations in Ca2+ transients (indo 1 fluorescence), indicating a decreased myofilament responsiveness to Ca2+. ANG II (100 nM) alone had no effect. However, ANG II with LPS produced higher cGMP levels (1,025 +/- 113 fmol/mg protein, n = 16, P < 0.05 vs. LPS alone), more severe contractile depression, impaired Ca2+ handling, and decreased mitochondrial activity (MTS assay). We conclude that ANG II and LPS have synergistic effects on the activation of NO-cGMP pathways to induce dose-dependent impairments in excitation-contraction coupling in cardiac myocytes.
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PMID:Angiotensin II exacerbates lipopolysaccharide-induced contractile depression in rabbit cardiac myocytes. 1033 Feb 26

To determine whether ANG II as well as mechanical stress affect the production of tumor necrosis factor (TNF) in the heart, neonatal rat cardiac myocytes and fibroblasts were cultured separately and treated for 6 h with ANG II, lipopolysaccharide (LPS), or cyclic mechanical stretch. LPS induced the production of TNF in cardiac myocytes and fibroblasts. However, TNF synthesis in fibroblasts was 20- to 40-fold higher than in myocytes. ANG II (>/=10(-8) M) and mechanical stretch stimulated the production of TNF in cardiac fibroblasts but not in myocytes. Furthermore, both ANG II and LPS increased the expression of TNF-alpha mRNA in cardiac fibroblasts. Isoproterenol inhibited both LPS- and ANG II-induced production of TNF in cardiac fibroblasts with increasing intracellular cAMP level. Moreover, both isoproterenol and dibutyryl cAMP inhibited LPS-induced TNF-alpha mRNA expression. Thus activation of the renin-angiotensin system, as well as mechanical stress, can stimulate production of TNF in cardiac fibroblasts. Furthermore, beta-adrenergic receptors may be responsible for the regulation of TNF synthesis at the transcriptional level by elevating intracellular cAMP.
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PMID:Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts. 1036 77

Expression of the inducible isoform of nitric oxide synthase (iNOS) and generation of nitric oxide (NO) have been recently described, in addition to mesangial and medullary thick ascending limb cells, in proximal tubular cells, including MCT, a mouse proximal tubular epithelium cell line. Because vasoconstrictors may interfere with the induction of iNOS and the subsequent generation of NO, in the study presented here, whether exogenous angiotensin II (ANG II) influences bacterial lipopolysaccharide (LPS)/gamma-interferon (gamma-IF)-stimulated NO synthesis and iNOS protein and mRNA expression in MCT cells was tested. LPS/gamma-IF readily stimulated nitrite synthesis in MCT cells, as one measured parameter of NO synthesis. Coincubation of cells with 10(-9)-10(-6) M ANG II attenuated this LPS/gamma-IF-stimulated induction of nitrite. This effect was reversed by the AT1-receptor blocker losartan, but not by an AT2-receptor antagonist, indicating signal transduction through AT1-receptors. Western blot analysis applying a specific monoclonal antibody generated against mouse iNOS revealed that 10(-8)-10(-6) M ANG II significantly reduced LPS/gamma-IF-induced iNOS protein expression. However, ANG II had no effect on LPS/gamma-IF-induced iNOS mRNA as assessed by Northern blots. Moreover, transient transfection studies using a chimeric gene construct, in which iNOS regulatory elements are linked to the CAT reporter gene, showed no effect of ANG II on the LPS/gamma-IF-stimulated transcriptional activity. The study presented here demonstrates that ANG II influences LPS/gamma-IF-stimulated NO generation in MCT cells, most likely at a posttranscriptional level, by influencing iNOS protein expression. Whether proximal tubular cells in vivo express iNOS remains to be established, but this study suggests a mechanism for how iNOS activity is influenced by ANG II in cultured proximal tubular cells.
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PMID:Angiotensin II inhibits inducible nitric oxide synthase in tubular MCT cells by a posttranscriptional mechanism. 1049 84

Angiotensin II (ANG II) and nitric oxide (NO) have contrasting vascular effects, yet both sustain inflammatory responses. We investigated the impact of ANG II on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced NO production in cultured rat mesangial cells (MCs). LPS/IFN-induced nitrite production, the inducible form of nitric oxide synthase (NOS-2) mRNA, and protein expression were dose dependently inhibited by ANG II on coincubation, which was abolished on ANG II type 2 (AT(2)) receptor blockade by PD-123319. Homology-based RT-PCR verified the presence of AT(1A), AT(1B), and AT(2) receptors. To shift the AT receptor expression toward the type 1 receptor, two sets of experiments were performed: LPS/IFN preincubation for 24 h was followed by 8-h coincubation with ANG II; or during 24-h coincubation of LPS/IFN and ANG II, dexamethasone was added for the last 6-h period. Both led to an amplified overall expression of NOS-2 protein and NO production that was inhibitable by actinomycin D in the first setup. Induced NO production was enhanced via the AT(1) receptor; however, it was diminished via the AT(2) receptor. In conclusion, induced NO production is negatively controlled by the AT(2), whereas AT(1) receptor stimulation enhanced NO synthesis in MCs. The overall NO availability depended on the onset of the inflammatory stimuli with respect to ANG II exposure and the available AT receptors.
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PMID:Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells. 1109 28

During endotoxic shock there is a dysfunction of the adrenal gland; both corticosterone and aldosterone secretion are altered. The aim of the present study is to use glomerulosa cells in primary culture as a target of lipopolysaccharide (LPS) action. Glomerulosa cells cultured in basal conditions are able to proliferate; bFGF and ACTH have antagonic effects, bFGF increases proliferation whereas ACTH is antimitogenic. LPS has a biphasic effect, in the short term it is antimitogenic and in the long term increases the proliferation rate. LPS inhibits ACTH-induced corticosterone secretion in a dose-dependent manner in glomerulosa cells in culture similar to that in fasciculata cells, but it does not exert an important direct effect on aldosterone secretion. These results show that LPS exerts different effects in ACTH and ANG II signal transduction pathways and in the two enzymes which catalyze the late step in the steroidogenesis, 11beta-hydroxylase and aldosterone synthase, which could be in agreement with the existence of both enzymes, regulated independently, in rat zona glomerulosa cells.
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PMID:Rat glomerulosa cells in primary culture and E. coli lipopolysaccharide action. 1279 60

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1beta production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1beta production in the rat brain induced by i.c.v. injection of LPS. LPS (0.2 and 2 microg i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1beta. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type 1 (AT(1)) receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1beta (i.c.v.)-induced fever, whereas the AT(1) receptor antagonist enhanced (rather than reduced) it. The AT(1) receptor antagonist had no effect on the brain levels of prostaglandin E(2) in rats given an i.c.v. injection of IL-1beta. These results suggest that in rats, brain ANG II and AT(1) receptors are involved in the LPS-induced production of brain IL-1beta, thus contributing to the fever induced by the presence of LPS within the brain.
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PMID:The effect of central injection of angiotensin-converting enzyme inhibitor and the angiotensin type 1 receptor antagonist on the induction by lipopolysaccharide of fever and brain interleukin-1beta response in rats. 1461 87

Angiotensin II (ANG II), a bioactive peptide that plays important roles in blood-pressure and body-fluid regulation, has recently been reported to be involved in normal thermoregulation and fever. In the case of thermoregulation, ANG II lowers body temperature when administered centrally or systemically (i.e. "exogenous" ANG II acts as a hypothermia-inducing agent). In contrast, "endogenous" ANG II is involved both in heat-loss responses in a hot environment and in thermogenesis in the cold. It therefore seems likely that endogenous ANG II is involved in maintaining body temperature at the set-point. In the case of fever, it has been reported that endogenous brain ANG II and its type 1 receptor mediate or modulate the fever induced by "restraint stress". At the final step in "pyrogen-induced" fever, brain ANG II facilitates the fever induced by prostaglandin E2 (PGE2) through its action on the type 2 receptor, whereas at its first step the lipopolysaccharide (LPS, 2 microg/kg, i.v.)-induced production of pyrogenic cytokines [such as interleukin-1 (IL-1)] involves an action of endogenous ANG II through its type 1 receptor. On the other hand, it is well known that a very high dose of LPS (50-5000 microg/kg) injected systemically induces hypothermia in rodents. This hypothermia is presumably initiated by tumor necrosis factor (TNF). Since ANG II contributes to the LPS-induced production of cytokines such as IL-1beta, as described above, it is possible that the generation of TNF by LPS involves an action of ANG II, too, and that this TNF production leads to the LPS-induced hypothermia. Together, these findings suggest that ANG II and its receptors make a number of contributions to normal thermoregulation, to fever, and to the hypothermia in systemic inflammation.
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PMID:Angiotensin II: its effects on fever and hypothermia in systemic inflammation. 1476 80

Angiotensin II (ANG II) activation of the angiotensin type 1 (AT1) receptor facilitates the production of brain interleukin-1beta (IL-1beta) and contributes to the induction of the fever following the intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). The purpose of the present study was to investigate whether proinflammatory transcription factors [nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1)] contribute to the ANG II-dependent production of cytokines within the brain. Interestingly, we found that a single i.c.v. injection of LPS had no effect on NF-kappaB and AP-1 activities in the hypothalamus, hippocampus, and cerebellum at either 1 or 3 h post-injection (except for a decrease in hypothalamic AP-1 activity at 1 h). Furthermore, both an angiotensin-converting-enzyme (ACE) inhibitor and an AT1 receptor antagonist enhanced (rather than reduced) the NF-kappaB and AP-1 activities in the hippocampus and/or cerebellum of rats given LPS. In contrast, an i.c.v. injection of ANG II increased the NF-kappaB activity in the hypothalamus. These results suggest that while "endogenous" ANG II exerts (via AT1 receptors) inhibitory effects on the activation of transcription factors in the brain of rats given LPS, a large dose of exogenous ANG II produces effects opposite to those induced by the presumably small amount of endogenous ANG II released locally by LPS. Our results seem not to support the idea that NF-kappaB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in the rat's brain.
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PMID:Effects of central injection of angiotensin-converting-enzyme inhibitor and angiotensin type 1 receptor antagonist on the brain NF-kappaB and AP-1 activities of rats given LPS. 1635 91


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