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)

In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity.
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PMID:Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat. 1838 67

The proposition that white adipose tissue is involved in the inflammatory response and metabolic dysregulation of endotoxaemia has been examined. Mice were injected with lipopolysaccharide (LPS; 25 mg/kg) and epididymal, perirenal and subcutaneous adipose tissue removed 4 or 24 h later. The expression of genes encoding key inflammation-related adipokines was measured by real-time polymerase chain reaction. At 24 h after the administration of LPS, there was no change in leptin mRNA level, and adiponectin mRNA fell. However, major increases in TNFalpha, MCP-1 (up to 40-fold) and IL-6 (up to 250-fold) mRNA levels were evident; a substantial elevation in these mRNAs occurred by 4 h, and adipose tissue IL-6 protein also increased (three- to eightfold). At 24 h, the responses in the subcutaneous depot were much lower than in epididymal and perirenal adipose tissue, but at 4 h, the subcutaneous tissue showed major increases in IL-6, MCP-1 and TNFalpha gene expression. In contrast to the inflammatory adipokines, the mRNA level of two macrophage markers, F4/80 and MAC-1, was unaltered in adipose tissue during endotoxaemia. Expression of the hypoxia-sensitive transcription factor, HIF-1alpha, gene was increased at both 4 and 24 h, and HIF-1alpha protein was elevated at 4 h, suggesting that the tissue was hypoxic. It is concluded that white adipose tissue may play an important role in the production of inflammatory mediators in endotoxaemia.
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PMID:Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice. 1867 10

The immune, endocrine and nervous systems are closely interrelated, which allows the organism to respond to different types of stress such as infection. Chronic infectious and inflammatory conditions are often accompanied by an impaired reproductive function. Leptin, a hormone produced by adipose tissue, exerts a regulatory function on the reproductive axis. It has homology with other proinflammatory cytokines and could be modified by lipopolysaccharide (LPS). Therefore, these studies were designed to investigate the effect of LPS administration on the neuroendocrine mechanisms involved in the regulation of the reproductive axis during sexual maturation. Fifteen- and 30-day-old female rats were injected with a single dose of LPS 250 microg/kg (i.p.) and then nitric oxide synthase (NOS) activity, hypothalamic excitatory/inhibitory amino acids and Gn-RH content, serum LH and leptin concentration were studied. In 15-day-old female rats LPS treatment did not modify hypothalamic inducible (iNOS) and constitutive (cNOS) NOS activity, Gn-RH, glutamate (GLU) and GABA content. Also serum LH and leptin levels were not modified. In 30-day-old rats LPS increased iNOS and cNOS activity (p < 0.001) and hypothalamic Gn-RH content (p < 0.001). At this age hypothalamic GABA content was significantly decreased (p < 0.001) without changes in GLU content, and serum LH (p < 0.001) and leptin (p < 0.0001) decreased significantly. In summary, current studies have demonstrated that LPS administration to 15- and 30-day-old female rats results in a different response of the hypothalamus-pituitary-gonadal axis and of the adipose tissue, demonstrating an ontogenic response of the immune-neuroendocrine system to LPS administration.
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PMID:Effect of bacterial lipopolysaccharide on the reproductive axis of prepubertal and peripubertal female rats. Ontogenic changes in the immune-neuroendocrine interactions. 1867 51

In order to imitate the in vivo situation with constituents from the blood-brain barrier, astrocytes from newborn rat cerebral cortex were co-cultured with adult rat brain microvascular endothelial cells. These astrocytes exhibited a morphologically differentiated appearance with long processes. 5-HT, synthetic mu-, delta- or kappa-opioid agonists, and the endogenous opioids endomorphin-1, beta-endorphin, and dynorphin induced higher Ca(2+) amplitudes and/or more Ca(2+) transients in these cells than in astrocytes in monoculture, as a sign of more developed signal transduction systems. Furthermore, stimulation of the co-cultured astrocytes with 5-HT generated a pronounced increase in intracellular Ca(2+) release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca(2+) responses were restored by opioids so that the delta- and kappa-opioid receptor agonists reduced the number of Ca(2+) transients elicited after incubation in substance P+CGRP or leptin, while the mu- and delta-opioid receptor agonists attenuated the Ca(2+) amplitudes elicited in the presence of LPS or leptin. In LPS treated co-cultured astrocytes the mu-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca(2+) transients. These results suggest that opioids, especially mu-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with mu-opioid receptors, also may act through some binding site on astrocytes, other than the classical opioid receptor.
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PMID:mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells. 1869 67

This study aimed to address the relative contributions of the proinflammatory cytokine interleukin-6 (IL-6) and the cytokine-like hormone leptin to the genomic activation of brain cells during lipopolysaccharide (LPS)-induced systemic inflammation. Wildtype and IL-6KO mice were injected with LPS (50 microg/kg, intraperitoneally) and the brains analyzed by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). LPS induced a pronounced nuclear translocation of the signal transducer and activator of transcription (STAT3) throughout the brains of wildtype mice, an effect that was significantly diminished, but not abolished, in the IL-6KOs. The remnant STAT3-activation, although still observed within some of the same areas activated by IL-6, was most intense in ependymal and meningial cells and along distinct blood vessels throughout the brain. This expression was almost totally abolished in the presence of an anti-leptin antiserum. Interestingly, the induction of cyclooxygenase 2 and microsomal prostaglandin E synthase (mPGES), the rate-limiting enzymes for synthesis of PGE2 by LPS, was diminished to a degree that correlated with the absence of IL-6 but not entirely with leptin. These results demonstrate that the induction of the inflammatory pathway in the brain is mediated by both IL-6 and leptin, which appear to work in tandem. Unlike IL-6, however, the contribution of leptin to this response was limited to distinct cell types/brain areas and STAT3-responsive target genes implicated in the brain-controlled sickness-type response. The physiological significance of leptin's action on meningeal and endothelial cells remains to be clarified but might reflect a role in LPS-induced immune cell infiltration into the brain.
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PMID:Selective contribution of interleukin-6 and leptin to brain inflammatory signals induced by systemic LPS injection in mice. 1880 40

The aim of this study was to investigate whether nicotine acetylcholine receptors (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with microvascular endothelial cells from adult rat brain, compared with monocultured astrocytes, as a sign of a more developed signal transduction system. Also investigated was whether nicotine plays a role in the control of neuroinflammatory reactivity in astrocytes. Ca(2+) imaging experiments were performed using cells loaded with the Ca(2+) indicator Fura-2/AM. Co-cultured astrocytes responded to lower concentrations of nicotine than did monocultured astrocytes, indicating that they are more sensitive to nicotine. Co-cultured astrocytes also expressed a higher selectivity for alpha7nAChR and alpha4/beta2 subunits and evoked higher Ca(2+) transients compared with monocultured astrocytes. The Ca(2+) transients referred to are activators of Ca(2+)-induced Ca(2+) release from intracellular stores, both IP(3) and ryanodine, triggered by influx through receptor channels. The nicotine-induced Ca(2+) transients were attenuated after incubation with the inflammatory mediator lipopolysaccharide (LPS), but were not attenuated after incubation with the pain-transmitting peptides substance P and calcitonin-gene-related peptide, nor with the infection and inflammation stress mediator, leptin. Furthermore, LPS-induced release of interleukin-1beta (IL-1beta) measured by enzyme-linked immunosorbent assay (ELISA) was more pronounced in co-cultured versus monocultured astrocytes. Incubation with both LPS and IL-1beta further attenuated nicotine-induced Ca(2+) response. We also found that LPS and IL-1beta induced rearrangement of the F-actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The rearrangements consisted of increases in ring formations and a more dispersed appearance of the filaments. These results indicate that there is a connection between a dysfunction of nicotine Ca(2+) signaling in inflammatory reactive astrocytes and upregulation of IL-1beta and the rearrangements of actin filaments in the cells.
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PMID:In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments. 1917 Nov 79

In vivo(1)H magnetic resonance spectroscopy (MRS) was used to examine the progression of fatty liver in two murine models of progressive hepatic steatosis: leptin-deficient obese (ob/ob) mice and mice maintained on a diet deficient in methionine and choline (MCDD). Ob/ob mice displayed high levels of intracellular hepatic triglycerides as early as 9 weeks after birth, as observed with MRS and histopathology. Single voxel spectra of ob/ob liver displayed strong resonances arising from saturated (1.3 ppm) and unsaturated (2.8 and 5.3 ppm) fatty acyl chains that could be resolved in the absence of water suppression. Hepatic inflammation, induced by lipopolysaccharide administration, led to a significant increase in unsaturated and polyunsaturated fatty acyl chain resonances (P<0.05), indicating a change in the composition of hepatic triglycerides in lipid droplets. Mice maintained on the MCDD displayed histological evidence of hepatic steatosis as early as two weeks, progressing to macrovesicular steatohepatitis at 10 weeks. The histological changes were accompanied by significant increases in saturated and unsaturated fatty acyl chain resonances and a significant decrease in the lipid/(water+lipid) ratio (P<0.05). These results indicate that in vivo(1)H MRS may be a suitable method to monitor the progression of steatohepatitis.
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PMID:In vivo assessment of hepatic triglycerides in murine non-alcoholic fatty liver disease using magnetic resonance spectroscopy. 1926 47

We recently reported that mouse astrocytes express leptin receptors (ObR), and that obesity induces upregulation of astrocytic ObR. To provide further evidence of the importance of astrocytic ObR expression, we performed double-labeling fluorescent in situ hybridization (FISH) and immunohistochemistry in the rat hypothalamus. Laser confocal microscopic image analysis showed that ObR mRNA was present in glial fibrillary acidic protein (+) cells that show distinctive astrocytic morphology as well as in neurons. In addition to the presence of ObR mRNA, ObR protein was shown in both astrocytes and neurons in the rat hypothalamus by double-labeling immunohistochemistry. In cultured rat C6 astrocytoma cells treated with different doses of lipopolysaccharide for 6h, the mRNA for ObRa or ObRb did not show significant changes, as measured by quantitative RT-PCR. However, the protein expression of both ObRa and ObRb, determined by Western blotting, was increased after the C6 cells were treated with either lipopolysaccharide or tumor necrosis factor-alpha. The results indicate that astrocytic ObR expression is present in rats as well as mice, and that it probably plays a role in the neuroinflammatory response.
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PMID:Leptin receptor mRNA in rat brain astrocytes. 1974 14

The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These 'adaptive' responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly mediated by neutrophil recruitment into the brain. We examined the contribution of leptin to this process in leptin-deficient (ob/ob), -resistant (db/db) and wild-type (WT) mice injected intraperitoneally with a septic dose of lipopolysaccharide (LPS). This treatment induced a dramatic increase in the number of neutrophils entering the brain of WT mice, an effect that was almost totally abolished in the mutant mice and correlated with a significant reduction in the mRNA levels of interleukin-1beta, intracellular adhesion molecule-1 and neutrophil-specific chemokines. These effects were reversed with leptin replenishment in ob/ob mice leading to recovery of neutrophil recruitment into the brain. Moreover, 48 h food deprivation in WT mice, which decreased circulating leptin levels, attenuated the LPS-induced neutrophil recruitment as did a single injection of an anti-leptin antiserum 4 h before LPS treatment in WT mice. These results provide the first demonstration that leptin has a critical role in leukocyte recruitment to the brain following severe systemic inflammation with possible implications for individuals with altered leptin levels such as during obesity or starvation.
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PMID:Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation. 1977 11

Recent evidence suggests that inflammation may be a common underlying cause of many obesity-associated conditions. To test whether obesity changes the response to inflammation, we investigated its effects on the acute phase of the inflammatory response to an endogenous pathogen, lipopolysaccharide (LPS). Diet-induced obese male Wistar rats exhibited an increased and prolonged fever response to LPS (100 microg/kg) relative to lean rats. LPS-treated obese rats also showed a greater increase in circulating TNF-alpha, IL-6, and IL-1 receptor antagonist within the first 8 h after LPS injection. LPS induced an increase in circulating leptin only in obese rats with no effect in lean rats. Analysis of expression of pyrogenic signaling in the hypothalamus demonstrated that obese rats show a greater increase in IL-1beta peaking at 2 h after LPS injection and suppressor of cytokine signaling 3 and IL-6 peaking at the 8-h time point. LPS-treated obese rats showed a significantly higher expression of IL-1 receptor antagonist in white adipose tissue (WAT) than lean rats, and WAT from obese rats incubated in LPS-supplemented medium (100 ng/ml) secreted a significantly higher level of IL-6. Overall, these results suggest that diet-induced obesity induces changes in the inflammatory response rendering the obese rats more responsive to the effects of LPS. These data also support the hypothesis that qualitative changes in WAT associated with obesity may contribute to these effects.
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PMID:Changes in hypothalamically mediated acute-phase inflammatory responses to lipopolysaccharide in diet-induced obese rats. 1979 20


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