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)

Injury to the vascular endothelium and the subsequent inflammatory response are considered prerequisites for the development of atherosclerosis. Platelet-derived growth factor (PDGF) production by and monocyte adhesion to aortic endothelial cells (EC) may participate in this inflammatory process and therefore are two potential targets for control by anti-inflammatory agents. Our previous studies have demonstrated that monocyte adhesion and PDGF production are stimulated by thrombin in EC. Here, we provide evidence that treatment of EC with the anti-inflammatory agent 3-deazaadenosine (c3Ado) effectively abolished thrombin-stimulated PDGF production and monocyte adhesion. c3Ado had no significant effect on either basal monocyte adhesion or constitutive PDGF production. c3Ado was also effective in negating monocyte adhesion induced by other agonists, such as interleukin-1, phorbol 12-myristate 13-acetate (PMA), and lipopolysaccharide. Northern analysis demonstrated that c3Ado significantly reduced thrombin- and PMA-stimulated steady-state levels of PDGF-A chain, PDGF-B chain, and endothelial-leukocyte adhesion molecule-1 (ELAM-1) mRNAs. Nuclear run-on studies demonstrated that a marked transcriptional activation of these genes by thrombin and PMA was abrogated by c3Ado treatment. The transcriptional rate of the alpha-tubulin gene was unaffected by the drug. Antibody binding studies with an anti-ELAM-1 monoclonal antibody 7A9 revealed that thrombin-stimulated EC expression of ELAM-1 was abolished by c3Ado, indicating that the suppression of ELAM-1 expression on EC surface may be a mechanism by which c3Ado interferes with monocyte adhesion. Experiments with the nucleoside transport inhibitor nitrobenzylthioinosine suggested that the transport of c3Ado into EC was required for its inhibitory activity. In addition, L-homocysteine thiolactone was found to potentiate the inhibitory activity of c3Ado, suggesting that the accumulation of intracellular c3Ado homocysteine may be the underlying mechanism by which c3Ado inhibits thrombin-induced EC function. Taken together, these results indicate that c3Ado may prove effective against vascular injury and inflammation through its ability to inhibit induction of both monocyte adhesion and PDGF production.
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PMID:3-Deazaadenosine inhibits thrombin-stimulated platelet-derived growth factor production and endothelial-leukocyte adhesion molecule-1-mediated monocytic cell adhesion in human aortic endothelial cells. 137 93

We have identified the metalloproteinase inhibitor TIMP-2 as a secreted product of human alveolar macrophages. In contrast to human fibroblasts, TIMP-2 was released from macrophages free of any apparent complexed metalloproteinases. Also in marked distinction to fibroblasts, TIMP-2 secretion from mononuclear phagocytes was subject to modulation by a variety of agents. TIMP-2 was synthesized by macrophages placed in culture under basal conditions in amounts approximately 30% of those secreted by fibroblasts on a per cell basis. The additions of lipopolysaccharide, denatured type I collagen, and zymosan to culture medium each resulted in a dose-dependent and profound decrease in macrophage TIMP-2 protein production and steady-state mRNA levels. In contrast, all of these agents markedly enhanced the biosynthesis of macrophage interstitial collagenase and TIMP-1 as assessed by analysis of identical cell and conditioned media samples. In human fibroblasts, TIMP-2 biosynthesis was unaffected by interleukin-1, tumor necrosis factor-alpha, platelet-derived growth factor, and phorbol ester despite the massive collagenase stimulation induced by each of these agents. We conclude that TIMP-2 is a potentially important mononuclear phagocyte product whose biosynthesis is regulated in a distinct and completely opposite manner to that of collagenase and TIMP-1.
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PMID:Identification of TIMP-2 in human alveolar macrophages. Regulation of biosynthesis is opposite to that of metalloproteinases and TIMP-1. 162 88

1. Platelet-derived growth factor (PDGF)-A and -B gene expression was studied in human monocytes. 2. Resting monocytes constitutively transcribed both PDGF-A and -B genes. When monocytes were stimulated by lipopolysaccharide (LPS), transcription rates of both genes were increased in a similar fashion. 3. Consistent with the transcription rates, resting monocytes constitutively expressed both PDGF-A and -B mRNAs. After LPS stimulation, the PDGF-A mRNA level increased gradually, while the PDGF-B mRNA level increased markedly and then decreased rapidly. 4. Reverse transcription-polymerase chain reaction showed that resting monocytes expressed only short PDGF-A mRNA species (representing exons I-V + VII), but LPS-stimulated monocytes expressed long PDGF-A mRNA species (representing exons I-VII) as well. Both resting and LPS-stimulated monocytes expressed only one PDGF-B mRNA species (representing exons I-VII). 5. Together these observations indicate that expression of PDGF-A and -B genes is differentially regulated at the levels of mRNA splicing and mRNA accumulation in monocytes, while transcription of both genes seems to be similarly controlled.
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PMID:Comparative studies on the platelet-derived growth factor-A and -B gene expression in human monocytes. 179 74

Alveolar macrophages (AM) recovered from the lower respiratory tract of individuals with interstitial lung disease (ILD) proliferate at a 2- to 15-fold increased rate (P.B. Bitterman et al. 1984. J. Clin. Invest. 74:460-469). Normal AM stimulated with immune complexes or asbestos release platelet-derived growth factor and insulin-like growth factor-I (IGF-I), and AM activated in vivo in ILD release these growth factors. We evaluated normal unstimulated and activated AM for the receptor for IGF-I to determine if macrophage IGF-I could be involved in the enhanced macrophage proliferation. Although normal AM did not have specific 125I-labeled recombinant IGF-I binding, AM activated by chrysotile asbestos or lipopolysaccharide in vitro or from individuals with ILD had detectable binding that could be inhibited by an anti-IGF-I receptor monoclonal antibody in a dose-dependent fashion. Autoradiography with 125I-labeled recombinant IGF-I revealed binding to the IGF-I receptor on the surface of activated AM, and the percentage of labeled cells was reduced with anti-IGF-I receptor monoclonal antibody or excess unlabeled recombinant IGF-I. Hybridization of total AM RNA to a 32P-labeled IGF-I receptor riboprobe using solution hybridization demonstrated IGF-I receptor mRNA transcripts in AM from an individual with asbestosis, consistent with active expression of the IGF-I receptor gene. In the context of the known role of IGF-I as a growth factor for many cells, these data are consistent with the concept that IGF-I and its receptor may play an important role in the proliferation of AM in the inflamed lower respiratory tract.
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PMID:Activated alveolar macrophages express the insulin-like growth factor-I receptor. 185 Jun 6

Platelet-derived growth factor (PDGF) is secreted by several cells that participate in the process of atherogenesis, including arterial wall monocyte-derived macrophages. Macrophages in human and non-human primate lesions have recently been demonstrated to contain PDGF-B chain protein in situ. In developing lesions of atherosclerosis, macrophages take up and metabolize modified lipoproteins, leading to lipid accumulation and foam cell formation. Oxidatively modified low density lipoproteins (LDL) have been implicated in atherogenesis and have been demonstrated in atherosclerotic lesions. The effects of the uptake of various forms of modified LDL on PDGF gene expression, synthesis, and secretion in adherent cultures of human blood monocyte-derived macrophages were examined. LDL oxidized in a cell-free system in the presence of air and copper inhibited the constitutive expression of PDGF-B mRNA and secretion of PDGF in a dose-dependent fashion. Oxidatively modified LDL also attenuated lipopolysaccharide-induced PDGF-B mRNA expression. These changes were unrelated to the mechanism of lipid uptake and the degree of lipid loading and were detectable within 2 h of exposure to oxidized LDL. The degree of inhibition of both basal and lipopolysaccharide-induced PDGF-B-chain expression increased with the extent of LDL oxidation. Monocyte-derived macrophages exposed to acetylated LDL or LDL aggregates accumulated more cholesterol than cells treated with oxidized LDL, but PDGF expression was not consistently altered. Thus, uptake of a product or products of LDL oxidation modulates the expression and secretion of one of the principal macrophage-derived growth factors, PDGF. This modulation may influence chemotaxis and mitogenesis of smooth muscle cells locally in the artery wall during atherogenesis.
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PMID:The influence of oxidatively modified low density lipoproteins on expression of platelet-derived growth factor by human monocyte-derived macrophages. 190 87

In the present study, we sought to identify the T cell-replacing factor which selectively induces IgG2b antibody formation in lipopolysaccharide-activated mouse spleen cells in vitro and in vivo, and which is present in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. The protein A plaque assay was used to measure IgM, IgG1, IgG2b, and IgG3 plaque-forming cells. An enzyme-linked immunosorbent assay was used to measure interleukin-6 (IL-6) levels in RA SF. We found that IgG2b induction by RA SF is not caused by IL-6, IL-1, or any other inflammatory cytokines or mediators, such as transforming growth factor beta, platelet-derived growth factor, nerve growth factor, fibroblast growth factor, epidermal growth factor, elastase, collagenase, and phospholipase A2. IgG2b-inducing factor in RA SF has unique biological properties compared with those of the interleukins and inflammatory mediators known to be present in RA SF.
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PMID:Relationship between IgG2b-inducing activity in rheumatoid arthritis synovial fluid and other well-known cytokines and inflammatory mediators. 195 23

Conditioned media from human peripheral blood leucocytes treated with lipopolysaccharide (LPS) induced a marked increase in the 3H-thymidine incorporation of cultured mesangial cells at low serum concentration (four to six times higher than control). Two sizes (100-70 and 8-12 kD) of monocyte-derived mesangial cell proliferating factors (MDF) were separated by column chromatography. Their peaks were distinct from those of thymocyte proliferating activity. The addition of anti-human interleukin-1 (IL-1) or anti-recombinant human interleukin-6 (IL-6) antibody to the fractionated MDF failed to have any effect on the mitogenic activity toward mesangial cells. The addition of anti-human platelet-derived growth factor (PDGF) antibody to the low molecular weight fraction decreased mesangial cell mitogenic activity (40-60% of control), but addition to the higher fraction did not (80-100% of control). From these data it seems that a large portion of the monocyte-derived mesangial cell growth factor was not comprised of IL-1 or IL-6 but of PDGF-like molecules; and that there is an unknown mesangial cell proliferating factor (or factors) besides IL-1, IL-6 and PDGF.
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PMID:Production by cultured human monocytes of mesangial cell proliferation factor(s) differing from interleukin-1 and interleukin-6. 198 27

Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF-beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF-beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.
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PMID:Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA. 212 46

Specific binding sites for human pancreatic secretory trypsin inhibitor (PSTI) on 3T3 Swiss albino cells were studied using radioiodinated recombinant PSTI. Some ion species, pH, and temperature significantly influenced the binding of 125I-PSTI. Kinetic studies showed that the binding of 125I-PSTI to 3T3 Swiss albino cells reached the maximum level within 120 min at 4 degrees C, with a slow dissociation rate. The half-maximal inhibition (ID50) of 125I-PSTI binding by unlabeled PSTI occurred at 1.0 x 10(-10) M. On Scatchard analysis of the competitive binding data, linear plots indicated a single class of receptors with high affinity (Kd = 5.3 x 10(-10) M) on 3T3 Swiss albino cells, the number of receptors being 5,400 per cell. Treatment of surface-bound radiolabeled PSTI with a chemical crosslinker (disuccinimidyl suberate) led to the identification of a membrane polypeptide of Mr 140,000 to which PSTI was crosslinked. The formation was inhibited by an excess amount of unlabeled PSTI in a dose-dependent manner. The binding of 125I-PSTI to 3T3 Swiss albino cells was competitively inhibited by unlabeled PSTI but not by other peptide hormones, such as epidermal growth factor (EGF), bovine fibroblast growth factor, insulin-like growth factor, transforming growth factor alpha, platelet-derived growth factor, and tumor necrosis factor, indicating the presence of receptors specific for PSTI. Various protease inhibitors had no or only a little effect, and mercaptoethanol and dithiothreitol strongly decreased the binding of 125I-PSTI. Incubation at 37 degrees C resulted in rapid internalization of cell-bound 125I-PSTI, followed by the appearance of trichloroacetic acid-soluble 125I-radioactivity in the culture medium, due to degradation of internalized PSTI. In addition, PSTI stimulated [3H]thymidine incorporation into DNA on 3T3 Swiss albino cells in a dose-dependent manner. The combined addition of PSTI and EGF stimulated [3H]thymidine incorporation to an extent greater than that seen with either agent alone. These results indicated that the biological effect of PSTI was mediated by high affinity plasma membrane receptors, which were not a cell-surface proteinase(s). Specific binding of 125I-PSTI was noted with the following cells: WI-38, 3T3 Swiss albino, HUVE, BDC-1, and H4-II-E-C3.
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PMID:Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor. 217 May 60

The effects of macrophage colony-stimulating factor (M-CSF or CSF-1) on the survival, proliferation, maturation and activation of human blood monocytes were examined. M-CSF (100-1,000 U/ml) doubled the number of monocytes surviving after eight days in culture and accelerated the usual increase in cell volume. Antiserum to M-CSF abolished both of these effects. There was no sizable increase in 3H-thymidine incorporation in monocytes over this time period. Of various factors tested, including gamma-interferon (gamma-IFN), interleukin (IL) 1 alpha, granulocyte CSF (G-CSF), platelet-derived growth factor (PDGF), and lipopolysaccharide (LPS), only granulocyte-macrophage CSF (GM-CSF) could also enhance survival and augment cell volume. While antiserum to human M-CSF eliminated the increase in survival induced by GM-CSF, it could not ablate the GM-CSF-stimulated increase in monocyte cell volume. Monocyte cell surface markers that increase with maturation (i.e., Fc gamma RIII) or with activation (i.e., Fc gamma RI) were unaffected by incubation with M-CSF.
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PMID:Examination of survival, proliferation and cell surface antigen expression of human monocytes exposed to macrophage colony-stimulating factor (M-CSF). 223 Feb 85


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