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)

Intercellular adhesion molecule 1 (ICAM-1) is a proinflammatory adhesion glycoprotein induced by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) as well as lipopolysaccharide (LPS). Little is known, however, concerning the intracellular regulatory mechanisms that modulate ICAM-1 expression in endothelial cells. We probed the involvement of protein kinase function and intracellular calcium ion upon ICAM-1 expression of human umbilical vein endothelial cells activated alternatively by TNF-alpha, IL-1 beta, LPS, or phorbol 12-myristate 13-acetate (PMA). Methodologies for the detection of ICAM-1 included both enzyme-linked immunosorbent assay and immunoprecipitation from biosynthetically labeled cells. The protein kinase inhibitor H-7 blocked induction of ICAM-1 by all of the activators; nonlinear regression analysis revealed 50% inhibitory concentration (IC50) values of 6-10 microM. Another kinase inhibitor, HA1004, did not block expression of the adhesion molecule at concentrations up to 50 microM. In contrast, the kinase inhibitor staurosporine dose dependently inhibited ICAM-1 expression triggered by PMA (IC50 67 +/- 4 nM) but, at similar concentrations, did not inhibit ICAM-1 expression induced by the other inflammatory stimuli. The divalent cation ionophore ionomycin (0.5 microM) interacted synergistically with PMA but not with cytokines or LPS in upregulating ICAM-1. We conclude from these data that although PMA-induced ICAM-1 expression may be triggered through activation of protein kinase C, ICAM-1 induction by IL-1 beta, TNF-alpha, or LPS may involve distinct regulatory pathway(s).
 ...
PMID:Discriminatory effects of protein kinase inhibitors and calcium ionophore on endothelial ICAM-1 induction. 134 98

The expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral endothelium was studied in primary cultures of human brain microvessel endothelial cells following treatment with bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Surface expression of ICAM-1 was examined with the immunogold silver staining technique. Intact cerebral endothelial cells constitutively express low levels of ICAM-1. Stimulation with LPS and cytokines induces upregulation of ICAM-1 which is minimal with IFN-gamma and maximal with LPS or a combination of IFN-gamma and TNF-alpha. Upregulation of ICAM-1 expression is concentration- and time-dependent, is observed as early as 4 h following incubation and persists for up to 72 h in the continuous presence of LPS or cytokines. The ICAM-1 expression is not reversed by 3 days after removal of the LPS or cytokines. These findings may be relevant to the interactions between leukocytes and brain microvessel endothelial cells in inflammatory and demyelinating diseases of the CNS.
 ...
PMID:Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. 135 10

Five clones derived from the same human malignant melanoma lesion were studied for their susceptibility to killing by human monocytes activated by exposure to interferon (IFN)-gamma and lipopolysaccharide. Melanoma clones were heterogeneous in their susceptibility to human monocyte cytotoxicity, with one clone (2/21) exhibiting extremely low levels of lysis. The different levels of susceptibility to monocyte cytotoxicity were not accounted for by susceptibility or resistance to monokines [tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6] because: (a) these effector molecules had little (TNF) or no (IL-1 and IL-6) cytolytic activity under these conditions; and (b) anti-TNF antibodies had marginal effects on cytotoxicity. Monocytes bound less to resistant than to susceptible melanoma cells. Monocyte-resistant 2/21 melanoma cells expressed substantially lower levels of ICAM-1 and VLA-4 than susceptible cells. Anti-CD18 and, to a lesser extent, anti-ICAM-1 mAb inhibited binding and cytotoxicity of human monocytes on malignant melanoma whereas anti-VLA-4 had no inhibitory action. Transfection of the ICAM-1 gene under the control of a constitutive promotor resulted in high levels of expression of ICAM-1 in 2/21 melanoma cells and, concomitantly, in augmented susceptibility to activated monocyte cytotoxicity. The augmented killing of ICAM-1 transfected 2/21 cells was inhibited by anti-ICAM-1 mAb. These results demonstrate that the CD18-ICAM-1 adhesion pathway can play an important role in the expression of human monocyte cytotoxicity on melanoma target cells and that heterogeneity in expression of ICAM-1 can underlie differences in susceptibility to tumoricidal activity.
 ...
PMID:Heterogeneous susceptibility of human melanoma clones to monocyte cytotoxicity: role of ICAM-1 defined by antibody blocking and gene transfer. 135 29

The intercellular adhesion molecule 1 (ICAM-1) is induced on endothelial cells by tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and lipopolysaccharide (LPS). We have reported the sensitivity of cytokine-induced ICAM-1 expression to protein kinase inhibitors, including inhibitors of protein kinase C (PKC) [C. L. Myers, S. N. Desai, J. Schembri-King, G. L. Letts, and R. W. Wallace. Am. J. Physiol. 262 (Cell Physiol. 31): C365-C373, 1992]. To directly investigate the role of PKC in ICAM-1 induction, we downregulated PKC by pretreatment of human umbilical vein endothelial cells with phorbol 12-myristate 13-acetate (PMA) and assessed ICAM-1 protein and mRNA induction elicited by subsequent exposure to inflammatory stimuli. PMA treatment results in ICAM-1 protein induction that declines to basal levels by 3 days. Western blots of endothelial cell lysates reveal a nearly complete loss of immunologically reactive PKC. Subsequent activation with cytokine or LPS leads to reinduction of ICAM-1 protein and mRNA; however, the cells no longer produced substantial amounts of ICAM-1 protein or mRNA in response to PMA stimulation. Cross desensitization is observed with phorbol dibutyrate, while 4 alpha-phorbol has no desensitizing effect. The data indicate that PKC activation, while capable of inducing ICAM-1 expression, is not essential for ICAM-1 induction by the inflammatory mediators TNF-alpha, IL-1 beta, or LPS.
 ...
PMID:Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC. 135 85

Leukosialin (CD43) is a sialic acid-rich molecule with a relative molecular mass (M(r)) of 140,000 highly represented on polymorphonuclear neutrophils (PMN) and on most leukocytes. One of its functions may be to prevent nonspecific cell-to-cell interactions through negative charge repulsions. As tested by immunofluorescence, neutrophil CD43 membrane expression was shown to decrease by up to 80% upon cell activation by phorbol myristate acetate (10 ng/ml) or by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10(-6) M) in the presence of cytochalasin B. The kinetic of this decrease paralleled that of CD11b up-regulation. FMLP alone, tumor necrosis factor (TNF-alpha), lipopolysaccharide and granulocyte macrophage colony-stimulating factor had moderate or insignificant effects, while inducing striking CD11b up-regulation. Cell priming with TNF-alpha followed by FMLP stimulation resulted in up to 40% decrease of CD43 expression. Anti-CD43 mAb immunoprecipitated three fragments of M(r) 130,000, 49,000 and 34,000 from the cell-free supernatant of activated neutrophils, suggesting that CD43 is released from the membrane by proteolysis. Indeed, the decrease in CD43 expression was inhibited by phenylmethanesulfonylfluoride (PMSF). Homotypic aggregation of activated PMN was also inhibited by PMSF and could result, at least in part, from the shedding of CD43. The shedding of such a strongly anionic and major membrane protein should drastically modify PMN surface charge and may allow previously hindered interactions by exposing new adhesion molecules.
 ...
PMID:Human neutrophils release their major membrane sialoprotein, leukosialin (CD43), during cell activation. 135 26

In the present article we show that supernatants derived from lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA)-stimulated A-20 B cell lymphoma are able to induce polyclonal immunoglobulin (Ig) secretion by normal B cells in a T-cell-dependent manner. This activity could be blocked by neutralizing monoclonal antibodies against interferon-gamma, but not by monoclonal antibodies against interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10 and granulocyte macrophage colony-stimulating factor (GM-CSF) or even a polyclonal antibody against tumor necrosis factor (TNF)-alpha. Furthermore, A-20 supernatants induced the production of measurable amounts of interferon-gamma by normal murine spleen cells and activates natural killer (NK) cells. Fractionation of factor-rich supernatants on a Sephacryl S-200 column revealed that the factor activity is located in the fractions corresponding to a molecular mass of 160-150 kDa and 80-70 kDa. The biological activities found in the A-20 supernatant are very similar to the ones described for the recently cloned human IL-12/NK cell stimulatory factor. These results suggest the existence of a murine analogous factor for the human IL-12 produced by A-20 B cell lymphoma.
 ...
PMID:An activated murine B cell lymphoma line (A-20) produces a factor-like activity which is functionally related to human natural killer cell stimulatory factor. 135 72

The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) in the pathobiochemistry of a number of clinical disorders underscores the need for a comprehensive understanding of the regulation of their expression. This study was undertaken to examine the effects of cytokines on XDH/XO activity and gene expression in pulmonary endothelial cells. The results indicate that IFN-gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells derived from both the microvasculature (LMVC) and the pulmonary artery. In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect. The increase in XDH/XO activity requires new protein synthesis. By Northern analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO gene. Transcriptional activation does not require new protein synthesis. The physiologic relevance of these observations was evaluated by administering IFN-gamma to rats. Intraperitoneal administration leads to an increased XDH/XO activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and biologically relevant inducer of XDH/XO expression; the major site of upregulation occurs at the transcriptional level.
 ...
PMID:Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. 137 Feb 94

Cytokine expression was analyzed in CD14++ regular monocytes and in the novel subset of CD14+/CD16+ small monocytes. Biologic activity for tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 in the supernatant of elutriator-enriched, cell sorter-purified small monocytes was about 10-fold lower compared with regular monocytes when stimulated with lipopolysaccharide (LPS) for 12 hours. In CD14++ regular monocytes levels were 1,157 U x 10(-3)/mL, 158 U/mL, and 1,337 U/mL for TNF, IL-1, and IL-6, respectively. By contrast, CD14+/CD16+ small monocytes exhibited 137 U x 10(-3)/mL, 14 U/mL, and 60 U/mL for TNF, IL-1, and IL-6, respectively. Additional treatment with interferon-gamma enhanced production of TNF in both subsets, but CD14+/CD16+ small monocytes still exhibited lower levels. Stimulation of the monocyte subsets by platelet-activating factor gave the same pattern of results. Hybridization with 32P-labeled oligonucleotides specific for the respective cytokine messenger RNAs (mRNAs) showed a 10-fold lower prevalence of transcripts for TNF, IL-1, and IL-6, as well. By contrast, the constitutive expression of Glyceraldehyde-3-phosphate-dehydrogenase mRNA was 1.7-fold higher in the CD14+/CD16+ small monocytes. These data indicate that the novel subset of small monocytes is selectively suppressed in the expression of the cytokines TNF, IL-1, and IL-6, suggesting that these cells may comprise a deactivated type of cell. The expression of class II transcripts in the small monocytes is, however, similar to the regular monocytes, and the cell surface expression of class II protein about threefold increased. Thus, the novel subset of small monocytes appears to be a functionally distinct type of cell.
 ...
PMID:Differential expression of cytokines in human blood monocyte subpopulations. 162 9

The kinetics of cytokine release and acute-phase protein gene expression in liver were investigated in rats receiving a single intraperitoneal bolus dose of Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, were measured by Northern blotting and were found to increase to a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a slower but more sustained rise. For albumin, hepatic mRNA was reduced, being minimum at 24 h with a similar but more prolonged fall in plasma concentration. Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we have defined an in vivo role of TNF-alpha in the control of endotoxin-induced acute-phase protein generation.
 ...
PMID:Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF-alpha monoclonal antibody. 137 42

We have investigated the role of the membrane molecules CD11/CD18 and CD14 which may mediate the binding of lipopolysaccharide (LPS) to human monocytes, in the induction of the production and release of interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) by LPS-stimulated cells. Blockade of CD11a, CD11b and CD18 with saturating concentrations of specific mAb did not inhibit the release of cytokines from LPS-stimulated monocytes. In contrast, inhibition of the release of IL-1 beta and TNF-alpha occurred in monocytes cultures that had been pretreated with either of two monoclonal antibodies (mAb) recognizing different epitopes on the CD14 molecule. The binding of LPS to CD14 has been previously shown to require serum factors. In the present study, we found that serum had an enhancing effect on the release of IL-1 and TNF-alpha from LPS-stimulated cultures of normal human monocytes. The inhibitory effect of anti-CD14 mAb was, however, observed in cultures performed in the presence or in the absence of serum, suggesting that triggering of IL-1/TNF-alpha release by CD14 is independent of LPS-binding proteins or other serum proteins. IL-1 beta and TNF-alpha were also released from LPS-stimulated cultures of monocytes from patients with paroxysmal nocturnal hemoglobinuria lacking expression of CD14. Thus, CD14 but not CD11/CD18 can trigger serum-dependent and independent cytokine release from endotoxin-stimulated normal human monocytes; CD14 is not, however, the only LPS receptor that is involved in the secretory response of endotoxin-stimulated cells.
 ...
PMID:Membrane molecules which trigger the production of interleukin-1 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated human monocytes. 137 58


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