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)

Expression of cytochromes P450 (CYP) is markedly reduced during inflammatory processes. In vitro studies with hepatocytes have shown that cytokines generated during these processes down-regulate CYP. However, it is not clear to what extent each individual cytokine contributes to the overall reduced expression of the various CYP isoenzymes in vivo. Interleukin 6 (IL-6), a major player during inflammatory processes, is recognized as the most important cytokine modulating the hepatic expression of acute-phase protein (APP) genes. For this reason, we selected the IL-6(-/-) mouse as a model to investigate the role of IL-6 in the down-regulation of hepatic CYP during experimental inflammation. Our results show that the reduction in messenger RNA (mRNA) levels of CYP1A2, CYP2A5, and CYP3A11 during turpentine-induced inflammation was abrogated in IL-6-deficient mice, confirming that IL-6 is an indispensable player for the down-regulation of hepatic CYP during aseptic inflammation. Moreover, the different CYP isoenzymes showed a variable grade of dependence on IL-6, CYP2A5 being the most sensitive one. In the case of CYP2E1, differences between IL-6(-/-) and wild-type mice were no longer maintained after 24 hours, suggesting a delayed, rather than abrogated, CYP down-regulation in the absence of IL-6. As opposed to that, hepatic CYP repression took place in IL-6-deficient mice during lipopolysaccharide (LPS)-mediated inflammation. This contrasting behavior observed for CYP is surprisingly similar to the one seen for extracellular (serum amyloid A, beta-fibrinogen) and intracellular (metallothionein-1) APPs and points to the fact that, in the model of bacterial inflammation (LPS), the effects of IL-6 on CYP down-regulation are likely to be substituted by other cytokines or mediators.
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PMID:Hepatic cytochrome P450 down-regulation during aseptic inflammation in the mouse is interleukin 6 dependent. 1086 88

IL-10-related T cell-derived inducible factor (IL-TIF or IL-21) is a new cytokine structurally related to IL-10 and originally identified in the mouse as a gene induced by IL-9 in T cells and mast cells. Here, we report the cloning of the human IL-TIF cDNA, which shares 79% amino acid identity with mouse IL-TIF and 25% identity with human IL-10. Recombinant human IL-TIF was found to activate signal transducer and activator of transcription factors-1 and -3 in several hepatoma cell lines. IL-TIF stimulation of HepG2 human hepatoma cells up-regulated the production of acute phase reactants such as serum amyloid A, alpha1-antichymotrypsin, and haptoglobin. Although IL-10 and IL-TIF have distinct activities, antibodies directed against the beta chain of the IL-10 receptor blocked the induction of acute phase reactants by IL-TIF, indicating that this chain is a common component of the IL-10 and IL-TIF receptors. Similar acute phase reactant induction was observed in mouse liver upon IL-TIF injection, and IL-TIF expression was found to be rapidly increased after lipopolysaccharide (LPS) injection, suggesting that this cytokine contributes to the inflammatory response in vivo.
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PMID:Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. 1095 42

Rat monoclonal antibodies (MoAbs) against mouse mannan-binding lectin (MBL)-A and MBL-C were generated and assays for MBL-A and MBL-C were constructed. This allowed for the quantitative analysis of both proteins for the first time. Previously only MBL-A has been quantified using less standardized methods. In a mouse serum pool the concentrations were now determined at 7.5 microg MBL-A and 45 microg MBL-C per ml. On gel permeation chromatography of mouse serum, MBL-A eluted corresponding to a M(r) of 850 kDa whereas the majority of MBL-C eluted corresponding to a Mr of 950 kDa. On sucrose density gradient centrifugation the sedimentation velocities of MBL-A and MBL-C were estimated at 7.3 S and 10.8 S, respectively. The MBL-A and MBL-C levels in 10 laboratory mice strains were compared and found to vary between 4 microg/ml to 12 microg/ml, and 16 microg/ml to 118 microg/ml, respectively. After the induction of acute phase responses by intraperitoneal injection of either casein or lipopolysaccharide (LPS), MBL-A was found to increase approximately two-fold, with a maximum after 32 h, while MBL-C did not increase significantly. In comparison, serum amyloid A component (SAA) peaked at 15 h with an approximate 100-fold increase.
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PMID:Characterization and quantification of mouse mannan-binding lectins (MBL-A and MBL-C) and study of acute phase responses. 1130 57

Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessive disorder featured by recurrent febrile attacks. Previous unpublished experience (J. van der Meer and R. Powell) suggested that thalidomide may prevent febrile attacks. Six HIDS patients (5 male and 1 female) who had at least one febrile attack every 6 weeks, entered a randomized, double-blind, placebo-controlled crossover trial to explore the efficacy of a daily 200-mg thalidomide dose in the treatment of recurrent febrile attacks of HIDS. The patients received either thalidomide, 200-mg daily, or placebo for 16 weeks, followed by a 4-week washout period and another 16-week treatment (crossover) with either thalidomide or placebo. Patients completed a weekly diary card noting attacks and side effects. During the study, C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist, soluble TNF receptor p55 and p75, and lipopolysaccharide-stimulated IL-1 beta and TNF-alpha production were measured at six different points, whereas urine neopterin levels were measured weekly. During the active treatment with thalidomide, there were 10 attacks compared with 13 attacks with placebo. Thalidomide resulted in a nonsignificant decrease of CRP and SAA, but the concentrations of other inflammatory mediators, including urine neopterin, remained unchanged. One patient developed sensory polyneuropathy, but this resolved when thalidomide administration was stopped. The effect of thalidomide in HIDS is limited to a decrease in acute phase protein synthesis without an effect on the attack rate.
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PMID:Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper-IgD and periodic fever syndrome: a randomized, double-blind, placebo-controlled trial. 1150 24

The host response to infection, the "acute phase response" is a highly conserved series of physiological reactions including marked changes in concentrations of plasma proteins. These proteins have been shown to participate in the immune response to infections. Several recent studies have elevated the role of acute phase proteins (APPs) as predictive markers in infection. APPs such as serum amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding protein (LBP) has certain biological functions in host defence and participates in acute phase reactions. We measured plasma levels of LBP in a group of 20 calves experimentally infected with Gram-negative Mannheimia haemolytica (Pasteurella) in comparison to haptoglobin, the most widely studied APP in cattle. In infected calves, LBP levels rose significantly 6 h after infection, reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after 12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove to be a diagnostic marker in cattle infection and is faster than haptoglobin in detecting sepsis.
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PMID:A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP). 1152 Oct 82

We have shown that leukemia inhibitory factor (LIF) and suppressor of cytokine signaling (SOCS)-3 are expressed in the hypothalamus and pituitary and that LIF induces proopiomelanocortin (POMC) and ACTH, whereas SOCS-3 abrogates corticotroph POMC gene transcription and ACTH secretion. Here, we determined the role of pituitary LIF and SOCS-3 in regulating hypothalamo-pituitary-adrenal (HPA) axis inflammatory responses. Murine pituitary LIF expression was induced up to eightfold after intraperitoneal injection of lipopolysaccharide or tumor necrosis factor-alpha, concordant with elevated plasma levels of ACTH and corticosterone. In LIF knockout (LIFKO) mice, induction of both ACTH and corticosterone were attenuated. LIF deletion was associated with elevated (P < 0.05) levels of pituitary TNF-alpha, interleukin (IL)-1beta, and IL-6 mRNA and cytokine-inducible pituitary SOCS-3 expression. Abrogation of the HPA axis stress response and higher pituitary levels of proinflammatory cytokines observed in LIFKO mice resulted in a stronger inflammatory process, as evidenced by elevated erythrocyte sedimentation rate and increased serum amyloid A levels (P < 0.05). The results indicate that, although LIF induces ACTH, SOCS-3 acts to counterregulate the HPA axis response to inflammation.
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PMID:Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation. 1193 77

We previously demonstrated epithelial induction of serum amyloid A in germ-free mice inoculated with luminal bacteria. The aims of the present study were to investigate the role of luminal bacteria and mucosal inflammation in epithelial expression of this acute-phase protein using germ-free and dextran sulfate sodium-treated mice in vivo and HT29 cells in vitro. Immunoreactivity for serum amyloid A was detected in the epithelium of esophagus, stomach, duodenum and rectum regardless of the presence or absence of luminal bacteria. Administration of dextran sulfate sodium resulted in colonic epithelial induction of serum amyloid A at the mRNA and protein levels in parallel with the progression of mucosal inflammation. Epithelial induction of serum amyloid A is possibly relevant to mucosal inflammation because that was observed in bacteria-reconstituted and dextran sulfate sodium-induced colitis in vivo and because interleukin-beta and lipopolysaccharide induced its mRNA in vitro.
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PMID:Epithelial induction of serum amyloid A in experimental mucosal inflammation. 1214 98

This work reports the effect of the apolipoproteins A-I and A-II (apoA-I and apoA-II) on the release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) and on the oxidative burst of human neutrophils. By themselves, apoA-I and apoA-II do not affect the basal liberation of these cytokines, whereas apoA-I affects the release of IL-1beta from lipopolysaccharide (LPS)-stimulated neutrophils and apoA-II affects IL-8 released from LPS-stimulated neutrophils. ApoA-II also decreases the production of IL-8 released by neutrophils stimulated with the acute phase apolipoprotein serum amyloid A. Both apoA-I and apoA-II exerted approximately 30% inhibition on the oxidative burst of neutrophils stimulated by opsonized zymosan, as revealed by the luminol-enhanced chemiluminescence assay. These findings give additional support to the idea that the role of human plasma lipoproteins and apolipoproteins goes beyond their function in lipid transport and metabolism. HDL apolipoproteins appear to be a class of mediators that can participate in the regulation of the activity of neutrophils.
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PMID:Apolipoproteins A-I and A-II downregulate neutrophil functions. 1245 30

In most mammalian species, serum amyloid A isoform 3 (SAA3) appears to be the predominant SAA isoform expressed extrahepatically. However, human SAA3 gene expression has not been detected previously and, therefore, this gene was referred to as a pseudogene. We report for the first time the transcriptional expression of human SAA3. Human SAA3 gene expression was detected by RT-PCR after stimulation of mammary gland epithelial cells with either prolactin (PRL) or lipopolysaccharide (LPS). The full-length 655bp cDNA sequence for this mammary-associated serum amyloid A3 (M-SAA3) was obtained using 5' and 3' rapid amplification of cDNA ends (RACE). The human M-SAA3 transcript would conceptually translate into a 42 residue mature protein, which is smaller than other mammalian SAA3 isoforms that are typically 104-113 amino acids in length. This study defines the cDNA sequence for human SAA3 and also demonstrates the upregulation of M-SAA3 expression in response to the lactational hormone PRL or to an acute phase stimulant such as LPS.
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PMID:Induction of human mammary-associated serum amyloid A3 expression by prolactin or lipopolysaccharide. 1258 16

Carp subjected to daily handling stress were much more susceptible to Trypanoplasma borreli infection than control fish. In a search for the cellular mechanisms involved, it was observed that cortisol suppressed T. borreli-induced expression of interleukin-1beta, tumor necrosis factor-alpha, serum amyloid A and inducible nitric oxide synthase. An NF-kappaB-inhibitor could replicate cortisol-induced apoptosis of activated peripheral blood leukocytes. In contrast, although this NF-kappaB-inhibitor induced apoptosis of neutrophilic granulocytes, cortisol prevented apoptosis of these cells, suggesting the latter process to be NF-kappaB-independent. Carp leukocytes, upon induction of apoptosis, exhibit a number of sequential metabolic alterations. First, the mitochondrial transmembrane potential (DeltaPsi(m)) is disrupted and glutathione levels are depleted, followed by exposure of phosphatidylserine on the outer cell membrane. In vitro, cortisol could inhibit NO production induced by low concentrations of lipopolysaccharide (LPS), but remarkably, enhanced NO production induced by high concentrations of LPS. However, no differences in NO production were observed in stressed versus non-stressed infected carp.
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PMID:Daily handling stress reduces resistance of carp to Trypanoplasma borreli: in vitro modulatory effects of cortisol on leukocyte function and apoptosis. 1259 Sep 74


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