Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute administration of cadmium results in hepatotoxicity. Recent reports indicate that Kupffer cells, the resident macrophages of the liver, participate in the manifestation of chemical-induced hepatotoxicity. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is a major product of Kupffer cells and mediates the hepatotoxic effects of lipopolysaccharide (LPS). It has been speculated that cadmium also may exert its hepatotoxicity via the production of TNF-alpha by the Kupffer cells. Therefore, this study was undertaken to determine whether mice deficient in TNF-alpha are resistant to Cd-induced hepatotoxicity. TNF-alpha-null (TNF-KO) and wild-type (WT) mice were dosed ip with saline, LPS (0.1 mg/kg)/Gln (d-galactosamine, 700 mg/kg), or CdCl2 (2.2, 2.8, 3.4, and 3.9 mg Cd/kg). Serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities were quantified to assess liver injury. Caspase-3 activity was quantified to assess hepatocellular apoptosis. LPS/Gln treatment increased ALT (17-fold) and SDH (21-fold) in WT mice. In contrast, LPS/Gln-treatment did not significantly increase ALT or SDH in TNF-KO mice. LPS/Gln-treatment caused a 7.8-fold increase in caspase-3 activity in WT mice but did not increase caspase-3 in TNF-KO mice. Cadmium caused a dose-dependent increase in liver injury in both WT and TNF-KO mice. However, the liver injury produced by Cd in the TNF-KO mice was not different from that in WT at any dose. No significant increase in caspase-3 activity was detected in any of the Cd-treated mice. These data indicate that, in contrast to LPS/Gln-induced hepatotoxicity, TNF-alpha does not appear to mediate Cd-induced hepatotoxicity.
 ...
PMID:Tumor necrosis factor-alpha-null mice are not resistant to cadmium chloride-induced hepatotoxicity. 1190 45

Hemodialysis patients exhibit a defective immune response leading to an increased susceptibility of infections and neoplasms. Far from being helpful, dialytic therapy per se also may be responsible for this acquired immunodeficiency. Dialysis membranes and bacterial products present in dialysis water may trigger and even perpetuate an abnormal mononuclear cell activation. Upon contact with cellulosic dialysis membranes, monocytes display an increased expression of surface markers of cell activation, such as adhesion molecules CD18, CD49, CD54 and the lipopolysaccharide (LPS) ligand (CD14). Moreover, proinflammatory cytokines as IL-1beta and TNF-alpha are released both in vivo and in vitro when monocytes are exposed to cellulosic membranes. Of special interest is the fact that end-stage renal disease patients undergoing hemodialysis exhibit an increased mononuclear cell apoptosis. This apoptosis is directly related to the degree of biocompatibility of the dialysis membrane. Apoptosis is activated when monocytes enter in contact with the cellulosic dialysis membrane through cell surface receptors linked to G-proteins. In early steps of apoptosis signaling, pertussis toxin-sensitive G proteins are coupled to protein kinase C (PKC)-dependent phosphorylative mechanisms. Furthermore, recent evidence support that the execution phase of apoptosis is mediated by a caspase-3 dependent pathway. Finally, very recent available data support that monocytes subjected to repeated activation suffer a process of accelerated senescence, as demonstrated by the senescent phenotype (CD14 and CD32) expressed and their shortened telomeric length. This senescent profile may generage a defective cellular response in acute stress situations, explaining (at least in part) the altered immune response observed in hemodialysis patients.
 ...
PMID:Cell apoptosis and hemodialysis-induced inflammation. 1198 20

Helicobacter pylori is a primary factor in the etiology of gastric disease, and its early pathogenic effects are manifested by up-regulation of inflammatory processes and the loss of mucus coat continuity. We investigated the role of extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) in the disturbances in gastric mucin synthesis and apoptotic processes evoked by H. pylori lipopolysaccharide (LPS). Exposure of gastric mucosal cells to the LPS led to a dose-dependent decrease (up to 59.5%) in mucin synthesis, accompanied by a marked increase in caspase-3 activity and apoptosis. Inhibition of ERK with PD98059 accelerated (up to 36.1%) the LPS-induced decrease in mucin synthesis, and caused further enhancement in caspase-3 activity and apoptosis. Blockade of p38 kinase with SB203580 produced reversal in the LPS-induced reduction in mucin synthesis, and substantially countered the LPS-induced increases in caspas-3 activity and apoptosis. Moreover, inhibition of caspase-3 blocked the LPS-induced increase in caspse-3 activity and produced an increase in mucin synthesis. Thus the detrimental influence of H. pylori LPS on gastric mucin synthesis is closely linked to caspase-3 activation and apoptosis, and involves ERK and p38 kinase participation.
 ...
PMID:Disruption in gastric mucin synthesis by Helicobacter pylori lipopolysaccharide involves ERK and p38 mitogen-activated protein kinase participation. 1205 97

Macrophages play an important role in the regulation of malignant tumors. Although glioma contains abundance of macrophages, their role in apoptosis of glioma is not known. We stimulated macrophages with lipopolysaccharide and culture supernatants of activated macrophages were collected to treat glioma cells. The results showed that molecules released from activated macrophages significantly increased apoptosis of glioma via Fas/FasL and caspase-3 pathways. The level of soluble Fas did not appear to be involved in the mechanism responsible for apoptosis seen in this study, as its level was barely detected in both experimental and control groups. Two cytokines, TNFalpha and IFNgamma, were significantly elevated in the supernatant obtained from the activated macrophages. Considering an important role of these two molecules in the induction of apoptosis mediated by the Fas/FasL system, the present data suggested that TNFalpha and IFNgamma were the main molecules to trigger the cascade of apoptotic reactions in glioma cells. In conclusion, the present study indicates that molecules released from the activated macrophages provide significant signals to stimulate the expression of Fas/FasL and caspase-3, which function to induce apoptosis in glioma cells.
 ...
PMID:Induction of apoptosis in glioma cells by molecules released from activated macrophages. 1212 80

Potential of sanguiin H-6, a component of Sanguisorbae Radix, to protect against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite (ONOO(-)) was examined using a model in which rats were injected with lipopolysaccharide (LPS) and then subjected to renal ischemia followed reperfusion (LPS plus ischemia-reperfusion). Ischemia-reperfusion was achieved by occluding bilateral renal artery for 60 min and then releasing for 350 min. At 50 min after ischemia started, LPS was injected intravenously. LPS plus ischemia-reperfusion induced a large amount of 3-nitrotyrosine, an oxidative product of protein that is produced via ONOO(-) nitration, which was not detectable in normal group. Oxidative damage of mitochondria was indicated by an accumulated thiobarbituric acid (TBA)-reactive substance, glutathione (GSH) depletion and glutathione peroxidase (GSH-Px) inactivation in the mitochondria. Treatment of rats with sanguiin H-6 (10 mg/kg body weight/day) for 30 days prior to LPS plus ischemia-reperfusion attenuated the oxidative damage in the mitochondria. The amount of TBA-reactive substance was decreased and the GSH levels significantly increased as compared with that in control group. However, its effect on GSH-Px activity was much weaker. Apoptosis induced by LPS plus ischemia-reperfusion was detected by fluorescence staining, TdT-mediated dUTP-biotin nick end labeling and electrophoretic analysis. Sanguiin H-6 appeared to inhibit apoptosis, and this was associated with the suppression of caspase-3 activity. These beneficial effects of sanguiin H-6 against oxidative damage in mitochondria and apoptosis contributed to the improvement in renal function by reversing the elevated levels of blood urea nitrogen and creatinine caused by ONOO(-).
 ...
PMID:Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo. 1218 96

Porphyromonas gingivalis is a Gram-negative periodontopathic bacterium colonizing the oral cavity and its lipopolysaccharide (LPS) is a key factor in the development of periodontitis. We investigated the effect of P. gingivalis LPS on the cellular responses associated with mucin synthesis in sublingual salivary gland acinar cells. Exposure of the acinar cells to the LPS led to a dose-dependent decrease in mucin synthesis and was accompanied by a massive induction in inducible nitric oxide synthase (NOS-2) activity and the increase in NO production, caspase-3 activity and apoptosis. Inhibition of extracellular signal-regulated kinase (ERK) with PD98059 accelerated the LPS-induced decrease in the glycoprotein synthesis and caused further increase in apoptosis and NOS-2 activity, while the blockade of p38 mitogen-activated kinase (MAPK) with SB203580 countered the LPS-induced reduction in the glycoprotein synthesis and obviated the induced increases in NOS-2 and apoptosis. Introduction of NOS-2 inhibitor, L-NAME, not only countered the LPS-induced increase in NO generation, caspase-3 activity and apoptosis, but caused the impedance of the LPS inhibition on mucin synthesis. The findings point to the upregulation in NOS-2 expression by P. gingivalis LPS as a key detrimental culprit affecting salivary mucin synthesis.
 ...
PMID:Porphyromonas gingivalis lipopolysaccharide interferes with salivary mucin synthesis through inducible nitric oxide synthase activation by ERK and p38 kinase. 1237 6

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H(2)O(2))-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H(2)O(2)-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.
 ...
PMID:Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. 1244 60

Monocytes are important components of the innate immune response. The number of circulating monocytes is controlled in part by apoptosis. We have previously shown that monocyte apoptosis requires the activation of caspase-3, a central component of the apoptotic machinery, and that several stimulatory signals, including endotoxin (lipopolysaccharide [LPS]), induce monocyte survival, by the inhibition of caspase-3. We hypothesized that the Th2 anti-inflammatory cytokine, interleukin (IL)-4, may also influence monocyte life span by modulating the apoptotic cascade and the kinases known to be activated by LPS. Here, we show that the IL-4-dependent killing of LPS-treated monocytes reactivates the apoptotic cascade blocked by endotoxin, evidenced by the activity of the effector caspase-3 and the upstream caspases-8 and -9. IL-4 did not affect the activity of caspase-3 or the fragmentation of DNA in nonstimulated monocytes, suggesting that the induction of the apoptotic cascade by IL-4 is specific for stimulated monocytes. In addition, we show that the ability of IL-4 to induce apoptosis is associated with the dephosphorylation of the extracellular signal-regulated kinase, but not with changes in TLR4 expression. Together, these findings suggest a molecular mechanism by which the anti-inflammatory cytokine IL-4 modulates the life span of monocytes at least in part by an extracellular signal-regulated kinase-dependent pathway.
 ...
PMID:Interleukin-4-induced apoptosis entails caspase activation and suppression of extracellular signal-regulated kinase phosphorylation. 1266 28

Increasing data provide support for the hypothesis that inflammatory cytokines mediate inflammation-induced injury to developing white matter. In the present study, roles of tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1beta) in mediating lipopolysaccharide (LPS)-induced brain injury were investigated by co-administration of LPS with IL-1 receptor antagonist (IL-1ra) or TNFalpha antibody in the 5-day-old rat brain. Intracerebral injection of LPS and other agents was performed in a stereotaxic apparatus at the location of 1.0 mm posterior and 1.0 mm lateral to the bregma, and 2.0 mm deep to the skull surface at the left hemisphere. Brain injury was examined in brain sections 3 and 11 days after LPS injection. LPS-induced inflammatory responses were evidenced by great increases in TNFalpha and IL-1beta concentrations in the neonatal rat brain 6 h after LPS injection. White matter rarefaction was observed in 71% (five out of seven) of the rat brains 3 days after LPS injection and bilateral ventricle dilation was found in 71% (five out of seven) of the P8 rat brains and in 100% of the P16 rat brains (four out of four). These alterations were not found in the control rat brains. No apparent histological changes in gray matter were observed in the LPS-injected rat brains. LPS injection also resulted in injuries to oligodendrocytes (OLs) and hypomyelination, as indicated by reduced immunostaining for O4 and myelin basic protein (MBP). Increased astrogliosis, as indicated by increased glial fibrillary acidic protein (GFAP) immunostaining, was also observed in the LPS-injected, but not the control rat brain. Co-administration of LPS with IL-1ra, but not with TNFalpha antibody, significantly attenuated LPS-induced white matter injury, as indicated by decreases in ventricle dilation, white matter rarefaction, GFAP positive staining and by improved O4 and MBP immunostaining. Co-administration of LPS with IL-1ra significantly reduced LPS-induced elevation of caspase-3 activity in the rat brain. While TNFalpha antibody had no effect on LPS-induced elevation of caspase-3 activity, co-administration of LPS with TNFalpha antibody partially, but significantly, decreased LPS-stimulated increase in IL-1beta in the neonatal rat brain. These data suggest that IL-1beta may play an important role in mediating LPS-induced brain injury and TNFalpha may have complicated, probably dual, effects in LPS-induced brain injury.
 ...
PMID:Differential roles of tumor necrosis factor-alpha and interleukin-1 beta in lipopolysaccharide-induced brain injury in the neonatal rat. 1276 91

Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by various stimuli. In this study, the effect of brefeldin A (BFA), which affects the biological process of secretion, on constitutive and delayed apoptosis of neutrophils was investigated. Neutrophil apoptosis was determined after culturing for 20 h in vitro by morphological changes, annexin V staining, and DNA electrophoresis. BFA dose-dependently increased the constitutive apoptotic rate of neutrophils. The delay of apoptosis induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) was also blocked by BFA. However, this effect of BFA was less marked when neutrophils were treated with dexamethasone, interleukin-8 (IL-8), or dibutyryl cAMP (dbcAMP). Moreover, the delay of neutrophil apoptosis induced by rottlerin, a specific inhibitor of protein kinase C (PKC)-delta, was significantly abrogated by BFA. Although BFA-induced apoptosis was not blocked by the caspase-3 inhibitor, zDEVD-fmk, myeloid cell leukemia-1 (Mcl-1) expression levels were downregulated by BFA. These results suggest that derangement of vesicular protein transport may be involved in the apoptosis of neutrophils, and that the action of BFA on apoptosis is dependent on changes in the expression of Mcl-1.
 ...
PMID:Modulation of constitutive and delayed apoptosis by brefeldin A in human neutrophils. 1278


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>