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)

During pregnancy, a local and systemic Th2 bias of maternal immunity favors Th1-dependent infections such as malaria. This study measured cytokines secreted in cultures of chorionic villi, placental blood cells (PBC), and serum in term placentas from 88 malaria-infected and -noninfected Cameroon women. Interleukin (IL)--2 and --4 were consistently low; IL-1 beta, IL-6, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)--beta 2 were highest in villi cultures. Tumor necrosis factor (TNF)--alpha, interferon (IFN)--gamma, and IL-10 were highest in PBC cultures. Malaria placental infection increased Th1-type cytokines, whereas Th2-type cytokines and TGF-beta 2 were unchanged. Addition of lipopolysaccharide or infected erythrocytes to cultures increased TNF-alpha, IL-1 beta, IL-6, and IL-10 secretions but not those of IFN-gamma and IL-4. Overall, Plasmodium falciparum induced a placental immune response involving both Th1- and Th2-type cell activation. Although the Th1 pathway was favored, IL-10 secretion was also increased, and this increase should be effective in protecting the placenta by controlling the negative effects of Th1 cytokines on pregnancy.
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PMID:Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta. 1131 91

Toxocara canis induces a predominantly Th2 type response with enhanced amounts of interleukin (IL)-4 and reduced amounts of interferon (IFN)-gamma in infected mice. In this study, we investigated the macrophage function of T. canis-infected mice from the standpoint of cytokine production. C3H/HeN mice were infected with T. canis by oral administration of embryonated eggs. Ten days after infection, macrophages were obtained from spleen and peritoneal cavity, were cultured with lipopolysaccharide, and cytokines in the culture supernatant were evaluated with enzyme-linked immunosorbent assay. Macrophages from T. canis-infected mice produced IL-1 and IL-6 equivalent to macrophages from normal mice. The production of IL-10 and tumour growth factor (TGF)-beta was enhanced, but IL-12 and tumour necrosis factor (TNF)-alpha production was diminished. The addition of IFN-gamma, anti-IL-10 antibody, anti-TGF-beta antibody or indomethacin did not restore the production of IL-12 and TNF-alpha by macrophages from T. canis-infected mice. Furthermore, the stimulation of normal macrophages with T. canis antigen in vitro induced IL-1alpha, IL-6, IL-10 and TGF-beta, but not IL-12 and TNF-alpha. These results indicate that cytokine producing pattern of macrophages is altered by T. canis-infection, and this altered macrophage function may play an important role in the modification of the immune response to T. canis.
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PMID:Suppression of macrophage interleukin-12 and tumour necrosis factor-alpha production in mice infected with Toxocara canis. 1141 83

We compared inflammatory responses to lipopolysaccharide (LPS) injection in laying type (Brown Nick) to broiler type (Avian x Avian) chicks. Rectal temperature was measured at 0, 1, 2, 4, 6, 12, and 24h after LPS injection (0, 0.1, 0.3, 0.6, 1, 2.5, or 5mg/kg bw). In layers, rectal temperature increased from 41.31+/-0.19 degrees C to a maximum 42.27+/-0.41 degrees C at 4h after 1mg/kg LPS. Relative to layers, the febrile response in broilers was considerably lower, delayed in onset, and required higher levels of LPS (5mg/kg). Proliferation of spleen cells from un-injected chicks in response to LPS, PHA, and Con A was evaluated in vitro. IFNgamma, TGFbeta(2), MGF and IL-1beta relative to beta-actin mRNA expression were analyzed in spleen cells stimulated with LPS. Splenocytes from layers had a higher proliferative response to LPS (P=0.045), but lower proliferative response to PHA (P=0.004) and Con A (P=0.004) than broilers. Expression of mRNA for MGF, IL-1beta and IFNgamma was lower in broilers than in layers (P<0.001). Reduced production of the pro-inflammatory cytokines in broilers could have resulted from the observed increased production of the immunosuppressive cytokine TGFbeta(2.) These differences in cytokine expression may explain the blunted febrile response in broilers compared to layers. Because the acute phase response of inflammation causes decreased food intake, the blunted inflammatory response of broilers may permit faster growth.
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PMID:Divergence of the inflammatory response in two types of chickens. 1147 84

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.
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PMID:Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines. 1149 Oct 15

This study examined, in human cancer lines, the pattern of cytokine production stimulated by lipopolysaccharide (LPS), a major component of outer surface of gram-negative bacteria, and characterized the expression pattern of CD14, cell surface LPS receptor antigen, and toll-like receptors (TLRs), which appear to be key regulators of the innate immune response system. Two colon cancer cell lines (DLD and LoVo), a hepatocellular carcinoma cell line and a myelomonocytic cell line were incubated with LPS for 0-72 h, and transforming growth factor (TGF) beta1 and beta2, hepatocyte growth factor (HGF) and interleukins 6, 8 and 15 were assayed. The only changes induced by incubation with LPS were significant increases in TGFbeta1 production at 12 h, and in HGF production at 72 h, in LPS-stimulated DLD cells, and significant increases in TGFbeta2 production after 12 h and in HGF after 72 h in LoVo cells. Using reverse transcriptase-polymerase chain reaction analysis, expression of CD14 and TLR-2 mRNA was detected in DLD and LoVo cells, and expression of TLR-4 mRNA was detected in PLC/PRF/5 and KG-1 cells. These results suggest that LPS induces TGFbeta and HGF production mediated by CD14/TLR-2 in cultured human colon cancer cell lines.
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PMID:Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells. 1172 28

The liver lobule is formed by parenchymal cells, i.e., hepatocytes and nonparenchymal cells. In contrast to hepatocytes that occupy almost 80% of the total liver volume and perform the majority of numerous liver functions, nonparenchymal liver cells, which contribute only 6.5% to the liver volume, but 40% to the total number of liver cells, are localized in the sinusoidal compartment of the tissue. The walls of hepatic sinusoid are lined by three different cell types: sinusoidal endothelial cells (SEC), Kupffer cells (KC), and hepatic stellate cells (HSC, formerly known as fat-storing cells, Ito cells, lipocytes, perisinusoidal cells, or vitamin A-rich cells). Additionally, intrahepatic lymphocytes (IHL), including pit cells, i.e., liver-specific natural killer cells, are often present in the sinusoidal lumen. It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring nonparenchymal cells. Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid. They perform important filtration function due to the presence of small fenestrations that allow free diffusion of many substances, but not of particles of the size of chylomicrons, between the blood and the hepatocyte surface. SEC show huge endocytic capacity for many ligands including glycoproteins, components of the extracellular matrix (ECM; such as hyaluronate, collagen fragments, fibronectin, or chondroitin sulphate proteoglycan), immune complexes, transferrin and ceruloplasmin. SEC may function as antigen-presenting cells (APC) in the context of both MHC-I and MHC-II restriction with the resulting development of antigen-specific T-cell tolerance. They are also active in the secretion of cytokines, eicosanoids (i.e., prostanoids and leukotrienes), endothelin-1, nitric oxide, and some ECM components. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytic and phagocytic capacity. They are in constant contact with gut-derived particulate materials and soluble bacterial products so that a subthreshold level of their activation in the normal liver may be anticipated. Hepatic macrophages secrete potent mediators of the inflammatory response (reactive oxygen species, eicosanoids, nitric oxide, carbon monoxide, TNF-alpha, and other cytokines), and thus control the early phase of liver inflammation, playing an important part in innate immune defense. High exposure of Kupffer cells to bacterial products, especially endotoxin (lipopolysaccharide, LPS), can lead to the intensive production of inflammatory mediators, and ultimately to liver injury. Besides typical macrophage activities, Kupffer cells play an important role in the clearance of senescent and damaged erythrocytes. Liver macrophages modulate immune responses via antigen presentation, suppression of T-cell activation by antigen-presenting sinusoidal endothelial cells via paracrine actions of IL-10, prostanoids, and TNF-alpha, and participation in the development of oral tolerance to bacterial superantigens. Moreover, during liver injury and inflammation, Kupffer cells secrete enzymes and cytokines that may damage hepatocytes, and are active in the remodeling of extracellular matrix. Hepatic stellate cells are present in the perisinusoidal space. They are characterized by abundance of intracytoplasmic fat droplets and the presence of well-branched cytoplasmic processes, which embrace endothelial cells and provide focally a double lining for sinusoid. In the normal liver HSC store vitamin A, control turnover of extracellular matrix, and regulate the contractility of sinusoids. Acute damage to hepatocytes activates transformation of quiescent stellate cells into myofibroblast-like cells that play a key role in the development of inflammatory fibrotic response. Pit cells represent a liver-associated population of large granular lymphocytes, i.e., natural killer (NK) cells. They spontaneously kill a variety of tumor cells in an MHC-unrestricted way, and this antitumor activity may be enhanced by the secretion of interferon-gamma. Besides pit cells, the adult liver contains other subpopulations of lymphocytes such as gamma delta T cells, and both "conventional" and "unconventional" alpha beta T cells, the latter containing liver-specific NK T cells. The development of methods for the isolation and culture of main liver cell types allowed to demonstrate that both nonparenchymal and parenchymal cells secrete tens of mediators that exert multiple paracrine and autocrine actions. Co-culture experiments and analyses of the effects of conditioned media on cultures of another liver cell type have enabled the identification of many substances released from non-parenchymal liver cells that evidently regulate some important functions of neighboring hepatocytes and non-hepatocytes. To the key mediators involved in the intercellular communication in the liver belong prostanoids, nitric oxide, endothelin-1, TNF-alpha, interleukins, and chemokines, many growth factors (TGF-beta, PDGF, IGF-I, HGF), and reactive oxygen species (ROS). Paradoxically, the cooperation of liver cells is better understood under some pathological conditions (i.e., in experimental models of liver injury) than in normal liver due to the possibility of comparing cellular phenotype under in vivo and in vitro conditions with the functions of the injured organ. The regulation of vitamin A metabolism provides an example of the physiological role for cellular cross-talk in the normal liver. The majority (up to 80%) of the total body vitamin A is stored in the liver as long-chain fatty acid esters of retinal, serving as the main source of retinoids that are utilized by all tissues throughout the body. Hepatocytes are directly involved in the uptake from blood of chylomicron remnants, and the synthesis of retinol-binding protein that transfers retinol to other tissues. However, more than 80% of the liver retinoids are stored in lipid droplets of hepatic stellate cells. HSC are capable of both uptake and release of retinol depending on the body's retinol status. The activity of some major enzymes of vitamin A metabolism have been found to be many times higher per protein basis in stellate cells than in hepatocytes. Despite progress in the understanding of the roles played by these two cell types in hepatic retinoid metabolism, the way in which retinoids move between the parenchymal cells, stellate cells, and blood plasma has not been fully elucidated. Sinusoidal blood flow is, to a great extent, regulated by hepatic stellate cells that can contract due to the presence of smooth muscle alpha-actin. The main vasoactive substances that affect constriction or relaxation of HSC derive both from distant sources and from neighboring hepatocytes (carbon monoxide, leukotrienes), endothelial cells (endothelin, nitric oxide, prostaglandins), Kupffer cells (prostaglandins, NO), and stellate cells themselves (endothelin, NO). The cellular cross-talk reflected by the fine-tuned modulation of sinusoidal contraction becomes disturbed under pathological conditions, such as endotoxemia or liver fibrosis, through the excess synthesis of vasoregulatory compounds and the involvement of additional mediators acting in a paracrine way. The liver is an important source of some growth factors and growth factor-binding proteins. Although hepatocytes synthesize the bulk of insulin-like growth factor I (IGF-I), also other types of nonparenchymal liver cells may produce this peptide. Cell-specific expression of distinct IGF-binding proteins observed in the rat and human liver provides the potential for specific regulation of hepatic IGF-I synthesis not only by growth hormone, insulin, and IGF-I, but also by cytokines released from activated Kupffer (IL-1, TNF-alpha, TGF-beta) or stellate cells (TGF-alpha, TGF-beta). Hepatic stellate cells may affect turnover of hepatocytes through the synthesis of potent positive as well as negative signals such as, respectively, hepatocyte-growth-factor or TGF-beta. Although hepatocytes seem not to produce TGF-beta, a pleiotropic cytokine synthesized and secreted in the latent form by Kupffer and stellate cells, they may contribute to its actions in the liver by the intracellular activation of latent TGF-beta, and secretion of the biologically active isoform. Many mediators that reach the liver during inflammatory processes, such as endotoxins, immune-complexes, anaphylatoxins, and PAF, increase glucose output in the perfused liver, but fail to do so in isolated hepatocytes, acting indirectly via prostaglandins released from Kupffer cells. In the liver, prostaglandins synthesized from arachidonic acid mainly in Kupffer cells in a response to various inflammatory stimuli, modulate hepatic glucose metabolism by increasing glycogenolysis in adjacent hepatocytes. The release of glucose from glycogen supports the increased demand for energetic fuel by the inflammatory cells such as leukocytes, and additionally enables enhanced glucose turnover in sinusoidal endothelial cells and Kupffer cells which is necessary for effective defense of these cells against invading microorganisms and oxidative stress in the liver. Leukotrienes, another oxidation product of arachidonic acid, have vasoconstrictive, cholestatic, and metabolic effects in the liver. A transcellular synthesis of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) functions in the liver: LTA4, an important intermediate, is synthesized in Kupffer cells, taken up by hepatocytes, converted into the potent LTC4, and then released into extracellular space, acting in a paracrine way on Kupffer and sinusoidal endothelial cells. Thus, hepatocytes are target cells for the action of eicosanoids and the site of their transformation and degradation, but can not directly oxidate arachidonic acid to eicosanoids. (ABSTRACT TRUNCATED)
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PMID:Cooperation of liver cells in health and disease. 1172 49

AIM:To study the regulatory effects of bacterial lipopolysaccharide (LPS) in murine macrophage proliferation.METHODS:Using murine peritoneal exudate macrophage (PEM) and macrophage cell line J(774) A.1 as targets, LPS effects on M-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated macrophage colony-forming cells (CFU-M) were detected. (125)I-GM-CSF receptor binding assay was used to examine LPS regulation on GM-CSF receptor expres-sion.RT-PCR was employed to test TGF-beta(1) inhibition on IFN-gamma mRNA expression on macrophage induced by LPS.RESULTS:Without direct effect on macrophage proliferation, LPS could inhibit the macrophage proliferation stimulated by GM-CSF.However,with the concomitant existence of GM-CSF and TGF-beta(1), the LPS inhibitory effect was eliminated.RT-PCR analysis indicated that the strongest mac-rophage growth inhibitory factor IFN-gammamRNA expression in macrophage induced by LPS was remarkably suppressed by TGF-beta(1), (125)I-GM-CSF receptor binding assay showed that LPS could enhance GM-CSF receptor expression likewise as TGF-beta(1).CONCLUSION:LPS is involved in the network of macrophage proliferative regulation by multiple cytokines, displaying inhibitory and stimulatory effects based on the coexisting cytokines.
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PMID:Regulatory effects of lipopolysaccharide in murine macrophage proliferation. 1181 57

Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis promastigotes. The downmodulation of NO production observed in infected and LPS-stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by decreased iNOS mRNA expression, suggesting that the parasite affects post-transcriptional events of NO synthesis. Supplementation with L-arginine or tetrahydrobiopterin did not increase NO production, suggesting that inhibition is not due to an insufficiency of substrate or co-factor. Treatment with anti-IL-10, anti-IL-4 or anti-TGF-beta neutralizing antibodies also failed to increase NO production, indicating that these cytokines are not involved in the observed parasite-induced inhibition of NO synthesis. However, treatment of the cultures with IFN-gamma resulted in a marked increase in NO production by infected LPS-stimulated cells. These results show that although L.(L.) amazonensis infection inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN-gamma is capable of overriding the suppression of NO synthesis.
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PMID:Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages. 1182 71

Matrix metalloproteinases (MMPs) and transforming growth factor (TGF)-beta are involved in airway remodeling associated with the inflammatory process. In this study, we investigated the effect of RP 73-401 (piclamilast), a selective phosphodiesterase-4 inhibitor, on MMP-9 activity and TGF-beta production in two murine models of acute inflammation. In the first model, the lipopolysaccharide (LPS)-induced increase in neutrophils, MMP-9 activity, and tumor necrosis factor (TNF)-alpha and TGF-beta release in bronchoalveolar lavage (BAL) was significantly reduced by RP 73-401 pretreatment. In contrast, the BAL interleukin (IL)-10 level was decreased by LPS but restored by RP 73-401. IL-10 administration in LPS-exposed mice elicited a significant reduction in BAL neutrophilia, MMP-9 activity, and TNF-alpha release but not in TGF-beta production. In the second model, RP 73-401 inhibited BAL neutrophils but not MMP-9 activity and TGF-beta production that were induced by intranasal TNF-alpha. We demonstrated that RP 73-401 might modulate the expression of airway remodeling-associated mediators such as MMP-9 and TGF-beta and that this effect seemed to be at least partially mediated by the balance between TNF-alpha and IL-10.
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PMID:The selective phosphodiesterase 4 inhibitor RP 73-401 reduced matrix metalloproteinase 9 activity and transforming growth factor-beta release during acute lung injury in mice: the role of the balance between Tumor necrosis factor-alpha and interleukin-10. 1190 82

When the brain suffers injury, microglia migrate to the damaged sites and become activated. These activated microglia are not detected several days later and the mechanisms underlying their disappearance are not well characterized. In this study, we demonstrate that interleukin (IL)-13, an anti-inflammatory cytokine, selectively induces cell death of activated microglia in vitro. Cell death was detected 4 days after the coaddition of IL-13 with any one of the microglial activators, lipopolysaccharide (LPS), ganglioside, or thrombin. This cell death occurred in a time-dependent manner. LPS, ganglioside, thrombin, or IL-13 alone did not induce cell death. Among anti-inflammatory cytokines, IL-4 mimicked the effect of IL-13, while TGF-beta did not. Cells treated with IL-13 plus LPS, or IL-13 plus ganglioside, showed the characteristics of apoptosis when analyzed by electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Electron micrographs also showed microglia engulfing neighboring dead cells. We propose that IL-13 and IL-4 induce death of activated microglia, and that this process is important for prevention of chronic inflammation that can cause tissue damage.
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PMID:Interleukin-13 and -4 induce death of activated microglia. 1200 40


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