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)

The in vitro effect of indomethacin (IM) and ibuprofen (IB) on the production of the interleukin-1 receptor antagonist (IL-1ra) by cord blood mononuclear cells (CBMC) from preterm newborns was compared to that of peripheral blood mononuclear cells (PBMC) from adults. Mononuclear cells (MC) were incubated with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IM and IB. The level of IL-1ra in the supernatants was tested by ELISA. The results showed a lower ability of MC from preterm newborns to produce IL-1ra as compared with adult cells, supporting the assumption of neonatal immune cell immaturity. IM at pharmacological concentrations caused inhibition of IL-1ra secretion by PBMC from adults whereas IB suppressed the secretion of IL-1ra at higher concentrations only. At the same concentrations neither drug had an in vitro effect on the production of IL-1ra by CBMC of preterm newborns. In conclusion, the lower ability of CBMC of preterm newborns to produce IL-1ra in response to LPS and the absence of an IM and IB effect on the secretion of this cytokine by these cells as compared with PBMC of adults, suggest an underdevelopment of the immune response in preterm newborns.
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PMID:Indomethacin and ibuprofen effect on IL-1ra production by mononuclear cells of preterm newborns and adults. 1216 27

A gene delivery system using bone marrow-derived CD11b(+)CD18(+) cells and their interaction with adhesion molecules was established. After transplantation into mice, these vehicle cells may be recruited into glomeruli upon lipopolysaccharide (LPS) treatment, and the number of recruited cells corresponds to the expression of intercellular adhesion molecule-1 (ICAM-1) in glomeruli. Using this system, interleukin-1 receptor antagonist (IL-1Ra) was delivered into animal models of glomerulonephritis evoked by anti-glomerular basement membrane antibody (anti-GBM nephritis). Urinary albumin excretion and the serum creatinine level were significantly elevated after anti-GBM antibody injection in mock-treated mice, whereas they were suppressed in the IL-1Ra-treated mice. Histological analysis revealed that glomerular injuries were also suppressed in IL-1Ra-treated mice. We further confirmed that specificity for inflamed glomeruli was significantly enhanced by a combination of the Cre/loxP system with the IL-1beta promoter. These data suggested that our novel system may be used as a therapeutic intervention for glomerulonephritis.
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PMID:Inflamed site-specific delivery of bone marrow-derived cells carrying IL-1Ra. 1238 2

Bilateral transection of the glossopharyngeal nerves (GLOx) disrupts the immune-to-brain communication from the posterior oral cavity. The current report tested whether this effect is due to the afferent (sensory) or efferent (parasympathetic motor) components of the nerve. Injection of lipopolysaccharide (LPS) into the soft palate (ISP) of GLOx or sham-operated (SHAM) rats increased the circulating levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra) and corticosterone (CORT), as well the hypothalamic content of IL-1beta; no difference in circulating levels and hypothalamic content was found between GLOx and SHAM at 2 and 4.5 h after LPS injection. These results indicate that glossopharyngeal neural efferents do not mediate the effects of GLOx on the immune-to-brain communication.
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PMID:Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation. 1262 Jun 48

The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. In this study, we examined the expression pattern of IL-1Ra and showed that it is highly expressed not only in liver and spleen, but also in white adipose tissue (WAT), where it is upregulated in obesity. In WAT of obese humans, IL-1Ra was also markedly increased. Moreover, human WAT explants secreted IL-1Ra into the medium, a process that could be stimulated fivefold by interferon-beta. Finally, lipopolysaccharide administration induced a long-lasting expression of IL-1Ra in mouse WAT, suggesting that adipose tissue is an important source of IL-1Ra in both obesity and inflammation. In summary, we demonstrated that WAT is one of the most important sources of IL-1Ra quantitatively, suggesting that this tissue could represent a novel target for anti-inflammatory treatment. Moreover, it can be speculated that IL-1Ra, whose production is markedly increased in WAT in obese individuals, contributes further to weight gain because of its endocrine and paracrine effects on the hypothalamus and adipocytes, respectively.
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PMID:Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation. 1271 39

1 This study examines the involvement of kinins in neutrophil migration into rat subcutaneous air pouches triggered by lipopolysaccharide (LPS), as well as the putative roles played by kinin B(1) and B(2) receptors, tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and selectins in this response. 2 LPS (5 ng to 10 micro g cavity(-1)) injected into the 6-day-old pouch induced a dose- and time-dependent neutrophil migration which peaked between 4 and 6 h, and was maximal following the dose of 100 ng cavity(-1) (saline: 0.46+/-0.1; LPS: 43+/-3.70 x 10(6) cells cavity(-1) at 6 h). 3 Bradykinin (BK) (600 nmol) injected into the pouch of saline-treated rats induced only modest neutrophil migration (0.73+/-0.16 x 10(6) cells cavity(-1)). A more robust response to BK (3.2+/-0.25 x 10(6) cells cavity(-1)) was seen in animals pretreated with captopril, but this was still smaller than the responses to IL-1beta or TNF-alpha (15 pmol: 23+/-2.2 x 10(6) and 75 pmol: 29.5+/-2 x 10(6) cells cavity(-1), respectively). Nevertheless, the B(1) agonist des-Arg(9)-BK (600 nmol) failed to induce neutrophil migration. 4 HOE-140 (1 and 2 mg kg(-1)), a B(2) receptor antagonist, reduced LPS-induced neutrophil migration. HOE-140 also reduced the neutrophil migration induced by BK, but had no effect on the migration promoted by IL-1beta or TNF-alpha. des-Arg(9)-[Leu(8)]-BK, B(1) receptor antagonist was ineffective in changing neutrophil migration caused by any of these stimuli. 5 Neutrophil migration induced by LPS or BK was reduced by interleukin-1 receptor antagonist (IL-1ra) (1 mg kg(-1)), sheep anti-rat TNF serum (anti-TNF serum) (0.3 ml cavity(-1)), and the nonspecific selectin inhibitor fucoidin (10 mg kg(-1)). 6 TNF-alpha levels in the pouch fluid were increased by LPS or BK injection, peaking at 0.5-1 h and gradually declining thereafter up to 6 h. IL-1beta levels increased steadily throughout the 6 h period. HOE-140 markedly inhibited the rise in IL-1beta and TNF-alpha levels in pouch fluid triggered by both stimuli. 7 These results indicate that BK participates importantly in selectin-dependent neutrophil migration into the air pouch triggered by LPS in the rat, by stimulating B(2) receptors coupled to synthesis/release of TNF-alpha and IL-1beta.
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PMID:Effect of a kinin B2 receptor antagonist on LPS- and cytokine-induced neutrophil migration in rats. 1277 Sep 32

The intestinal flora play an important role in experimental colitis and inflammatory bowel disease (IBD). Using colonic explant cultures from 132 IBD and control subjects, we examined tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and interleukin-1 receptor antagonist (IL-1RA) production in vitro in response to bacterial activators. Unstimulated TNF-alpha release was increased significantly in rectal biopsies from involved IBD tissue, correlating with inflammation severity. Whereas lipopolysaccharide (LPS) only moderately stimulated TNF-alpha production from inflamed tissue, pokeweed mitogen (PWM) induced its release in all groups, with a stronger response in involved IBD tissue. Superantigen staphylococcal enterotoxin A (SEA) had a similar, but weaker effect. SEB was observed to be the strongest inducer of TNF-alpha for all groups, again with a more marked response in inflamed tissue. Stimulated release of IL-1 was considerably less than for TNF-alpha. The superantigens' superior potency over LPS was not as marked for IL-1 as it was for TNF-alpha. In addition to IL-1, IL-1RA release was also triggered by the bacterial products. The net effect of activation on the IL-1RA/IL-1 ratio was relatively modest. Release of the proinflammatory cytokines TNF-alpha and IL-1, as well as that of the anti-inflammatory cytokine IL-1RA was increased by incubation of colonic tissue with bacterial factors. TNF-alpha production and release was increased significantly in involved colonic explants from IBD. SEB was even capable of inducing TNF-alpha release from uninvolved colonic tissue.
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PMID:Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease. 1282 84

It is established that the molecular chaperone, chaperonin 60, from various bacteria and from Homo sapiens has cell-cell signalling activity and is able to induce proinflammatory cytokine synthesis. We previously reported that chaperonin 60 proteins from Gram-negative bacteria, but not mycobacteria, have the capacity to resorb cultured murine calvarial bone. We now report that lipopolysaccharide-low human recombinant chaperonin 60 (Hsp60) is a relatively weak cytokine-inducing agonist but is a potent stimulator of murine calvarial bone resorption. The osteolytic activity of Hsp60 was significantly inhibited by indomethacin, interleukin-1 receptor antagonist, and osteoprotegerin, but 5-lipoxygenase inhibitors were less effective. Analysis of Hsp60 truncation mutants revealed that N-terminal mutants (Delta1-137, Delta1-358, and Delta1-465) retained bone resorbing activity. In contrast, a C-terminal truncation mutant (Delta1-26 + Delta466-573) was inactive. This suggests that the active domain in this protein is found within residues 466-573. It is now established that Hsp60 is present in the blood of the majority of the population with the normal range encompassing levels able to activate bone cells. The possibility exists that this protein could play a role in bone remodelling.
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PMID:Human chaperonin 60 (Hsp60) stimulates bone resorption: structure/function relationships. 1367 84

Rats have an attenuated febrile response to exogenous (e.g. bacterial endotoxin) and endogenous pyrogen (e.g. interleukin-1beta) near the term of pregnancy, the mechanism of which is unknown. The present experiments were carried out on 71 non-pregnant and 181 pregnant Sprague-Dawley rats to determine if basal levels of the endogenous antipyretic substance, interleukin-1 receptor antagonist (IL-1ra), change relative to interleukin-1beta (IL-1beta) throughout gestation. Furthermore, we have constructed complete Escherichia coli lipopolysaccharide (LPS) dose-core temperature response curves in non-pregnant and pregnant rats on days 10, 15 and 20 of gestation (term of gestation approximately 21 days) to determine if the attenuated febrile response near the term of pregnancy results from a simple shift of the dose-response relationship or results from a dampening of the overall dose-response relationship. Basal IL-1beta, as determined by ELISA on trunk blood from non-pregnant and pregnant rats on days 10, 15 and 20 of gestation (d10, d15, d20), did not change significantly during pregnancy. Basal IL-1ra, however, was increased significantly in d15 rats as compared to non-pregnant, and d10 and d20 rats. The attenuated febrile response near the term of pregnancy, as determined by biotelemetry, did not result from a simple shift of the E. coli LPS dose-core temperature response curve but rather a dampening of the overall dose-response relationship. The febrile responses to EC(50) and EC(100) doses of E. coli LPS were preceded by a period of hypothermia, and were delayed and attenuated near the term of pregnancy as compared to that observed early in pregnancy and in non-pregnant rats. Our data provide evidence that pregnant rats are more sensitive to the hypothermia-producing effects of E. coli LPS than are non-pregnant rats and allow us to speculate that elevated basal IL-1ra may play a role in mediating the attenuated febrile response to pyrogen on day 15 but not on day 20 of gestation in rats.
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PMID:Influence of pregnancy on plasma cytokines and the febrile response to intraperitoneal administration of bacterial endotoxin in rats. 1460 73

The extent to which bacterial products from contaminated dialysate enter a patient's blood depends upon the type and permeability of the hemodialysis membrane in use. This study was performed to assess the transfer of pyrogenic substances across both high- and low-flux membranes (DIAPES, Fresenius Polysulfone, Helixone, Polyamide S). All experiments were carried out in the saline-saline model. The dialysate pool was contaminated either with purified lipopolysaccharide (LPS) (250 and 500 EU/mL) or with sterile bacterial culture filtrates (20 EU/mL), and in vitro dialysis was performed under diffusive and convective conditions. A significant transfer of endotoxin was observed for both low- and high-flux DIAPES challenged with either LPS or with bacterial culture filtrates. Under identical conditions, no transfer of endotoxins was detectable across Fresenius Polysulfone and Helixone upon challenge with purified LPS. With bacterial culture filtrates, endotoxin concentrations for Polyamide S and Fresenius Polysulfone were about 10% and 1%, respectively, of those measured for DIAPES, whereas no transfer of endotoxin was detectable for Helixone. Using an alternative assay (induction of interleukin-1 receptor antagonist, IL-1Ra, in whole blood), only the DIAPES membrane showed the passage of cytokine-inducing substances. Thus, when saline is present in both the blood and dialysate compartments (i.e., the situation during predialysis priming procedures), dialysis membranes differ profoundly with respect to their permeability to endotoxins.
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PMID:Pyrogen transfer across high- and low-flux hemodialysis membranes. 1496 61

Rats have an attenuated febrile response to intraperitoneal (i.p.) administration of exogenous pyrogen (e.g. bacterial endotoxin) near the term of pregnancy. To investigate possible mechanisms of this unique thermoregulatory response, the present experiments were carried out on 18 non-pregnant and 16 near-term pregnant Sprague-Dawley rats to test the hypothesis that pregnancy alters the balance of pyrogenic cytokines and antipyretic and/or cryogenic (antipyretic/cryogenic) cytokines in response to exogenous pyrogen. To test our hypothesis, we measured plasma levels of interleukin (IL)-1beta, IL-6, interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor alpha(TNFalpha) at 2 and 4 h following i.p. administration of 160 microg kg(-1) E. coli lipopolysaccharide (LPS) (i.e. EC100 dose, or the smallest dose that elicits a maximal febrile response in non-pregnant rats) in non-pregnant as well as pregnant rats at day 20 of gestation (term approximately 21 days). In non-pregnant rats, E. coli LPS elicited statistically significant increases in plasma concentrations of IL-1beta, IL-6, IL-1ra and TNFalpha as compared to that observed following administration of vehicle. However in pregnant rats, E. coli LPS elicited statistically significant increases in antipyretic/cryogenic cytokines (IL-1ra and TNFalpha) but not in pyrogenic cytokines (IL-1beta and IL-6). Thus, a differential pyrogenic and antipyretic/cryogenic plasma cytokine response may mediate in part the attenuated febrile response to exogenous pyrogen observed in rats near the term of pregnancy.
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PMID:Pregnancy influences the plasma cytokine response to intraperitoneal administration of bacterial endotoxin in rats. 1546 57


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