UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF-alpha) has been shown to play an important role in local control of bone remodeling. The interaction of TNF-alpha and PTH was evaluated in UMR-106-01 cells, a phenotypic osteoblastic osteosarcoma cell line. We examined the influence of TNF-alpha on the two signal transduction systems triggered by PTH in UMR-106-01 cells, adenylate cyclase and free cytosolic calcium ([Ca2+]i). cAMP generation was inhibited in TNF-alpha-pretreated cells by 69, 61, 34, and 21% at PTH concentrations of 0.1, 1, 10, and 100 nM, respectively. Inhibition was seen at TNF-alpha doses of 100-1500 units/ml after a minimum incubation time of 12 h. TNF-alpha inhibition of the PTH-stimulated increase in [Ca2+]i was even more pronounced: treated cells showed no change in baseline [Ca2+]i after stimulation with 40 nM PTH. Treatment with TNF-alpha was also found to inhibit both arms of the PTH response in the nontransformed osteoblastic cell line, MC3T3-E1. TNF-alpha treatment did not alter cAMP generation in response to PGE2. TNF-alpha inhibition of the PTH-stimulated cAMP response was reversed completely by addition of cholera toxin (5 micrograms/ml) and partially by forskolin (10 microM) but not pertussis toxin (100 and 500 ng/ml). Scatchard analysis using PTHrP revealed that TNF-alpha treatment reduced the number of receptors but had no effect on KD. These findings suggest that TNF-alpha inhibits the osteoblastic response to PTH at least in part because of a reduction in receptor number. Further investigation is indicated to provide insight into the interaction of calciotropic hormones and cytokines in vivo.
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PMID:Tumor necrosis factor alpha modulates parathyroid hormone action in UMR-106-01 osteoblastic cells. 825 56

We have examined the role of Gi alpha in haemopoietic cells using the myelomonocytic progenitor cell lines FDC-P1 and WEHI-3B (JCS). During growth factor-dependent proliferation of FDC-P1 cells Gi alpha was found predominantly in the nucleus and associated with the plasma membrane. Following removal of growth factor, Gi alpha accumulated in the cytoplasm and at the plasma membrane. Treatment of FDC-P1 cells with pertussis toxin (PT) completely inhibited translocation of Gi alpha to the nucleus and reduced the sensitivity of FDC-P1 cells to the proliferative effects of growth factors, indicating that translocation of Gi alpha plays a regulatory role in, but may not be essential for, cell division. Gi alpha initially associated with DNA during S/G2 of the FDC-P1 cell cycle but separated from condensing chromosomes during mitosis. In contrast to FDC-P1 cells, WEHI-3B (JCS) cells proliferate in the absence of added growth factors but can be induced to differentiate by TNF-alpha. In proliferating JCS cells Gi alpha was again associated with the nucleus but when proliferation was inhibited by TNF-alpha, Gi alpha accumulated in the cytoplasm with none detected in the nucleus. Thus the cytokine regulated accumulation of Gi alpha at different intracellular sites correlated with the ability of the cell to progress through the proliferative cycle. When the tyrosine kinase inhibitor genistein was added to FDC-P1 cells prior to stimulation with IL-3 or GM-CSF, proliferation was almost completely inhibited but translocation of Gi alpha was not affected, suggesting that tyrosine phosphorylation was not involved in G protein translocation but was essential for cytokine induced cell division. Cholera toxin (CT) also inhibited proliferation of FDC-P1 cells but had no effect on translocation of Gi alpha to the nucleus. The near complete inhibition of cell division by genistein and CT without a corresponding effect on Gi alpha movement indicates that Gi alpha can be regulated independently of tyrosine kinase and adenylyl cyclase activities, respectively.
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PMID:Localization of the GTP-binding protein Gi alpha in myelomonocytic progenitor cells is regulated by proliferation (GM-CSF, IL-3) and differentiation (TNF) signals. 834 49

It has been established that LPS, the major constituent of the outer membrane of gram negative bacteria, stimulates macrophages to produce numerous inflammatory mediators, including TNF-alpha and nitric oxide (NO). Both TNF-alpha and NO are important in the macrophage-mediated cytotoxicity against invading microorganisms and tumor cells. Although many LPS-dependent immune responses have been well characterized phenomenologically, the precise signal transduction pathways in LPS-induced macrophage activation are not clear. We reported that 1) pretreatment of C3HeB/FeJ mouse peritoneal macrophages with pertussis toxin (PT) markedly enhanced LPS-induced TNF-alpha production but inhibited LPS-dependent NO production under the same conditions; 2) kinetics of the PT effects on these LPS-responses were correlated with PT-mediated ADP-ribosylation of a 41-kDa protein(s); and 3) PT pretreatment did not correct the refractory states of C3H/HeJ macrophages to wild type smooth-LPS. These results suggest that LPS stimulates TNF-alpha and NO production in mouse peritoneal macrophages through different biochemical pathways, and that the signal transduction for both pathways is regulated by a PT-sensitive factor. It is possible that this factor is a guanine nucleotide-binding regulatory protein(s). Finally our data indicate that it is unlikely that the defect of the C3H/HeJ macrophages in response to LPS is at the level of this PT-sensitive factor.
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PMID:Pertussis toxin-sensitive factor differentially regulates lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production in mouse peritoneal macrophages. 842 28

To elucidate the role of specific proinflammatory cytokines in regulating airway responsiveness, we examined the effects and mechanisms of action of IL-1beta, TNF-alpha, and IL-2 on the beta-adrenoceptor- and postreceptor-coupled transmembrane signaling mechanisms regulating relaxation in isolated rabbit tracheal smooth muscle (TSM) segments. During half-maximal isometric contraction of the tissues with acetylcholine, relaxation responses to isoproterenol, PGE2, and forskolin were separately compared in control (untreated) TSM and tissues incubated for 18 h with IL-1beta (10 ng/ml), TNF-(alpha (100 ng/ml), or IL-2 (200 ng/ml). Relative to controls, IL-1beta- and TNF-alpha-treated TSM, but not IL-2-treated tissues, depicted significant attenuation of their maximal relaxation and sensitivity (i.e., -log dose producing 50% maximal relaxation) to isoproterenol (P < 0.001) and PGE2 (P < 0.05); whereas the relaxation responses to direct stimulation of adenylate cyclase with forskolin were similar in the control and cytokine-treated tissues. Further, the attenuated relaxation to isoproterenol and PGE2 was ablated in the IL-1beta-treated TSM that were pretreated with either the muscarinic M2-receptor antagonist, methoctramine (10(-6) M), or pertussis toxin (100 ng/ml). Moreover, Western immunoblot analysis demonstrated that: (a) Gi protein expression was significantly enhanced in membrane fractions isolated from IL-1beta-treated TSM; and (b) the latter was largely attributed to induced enhanced expression of the Gi alpha2 and Gi alpha3 subunits. Collectively, these observations provide new evidence demonstrating that IL-lbeta and TNF-alpha induce impaired receptor-coupled airway relaxation in naive TSM, and that the latter effect is associated with increased muscarinic M2-receptor/Gi protein-coupled expression and function.
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PMID:Mechanism of cytokine-induced modulation of beta-adrenoceptor responsiveness in airway smooth muscle. 864 53

In this study, we examined the effect of TNF-alpha on mesangial cell gene expression of M-CSF, a colony-stimulating factor associated with monocyte differentiation into macrophages and proliferation. Incubation of mesangial cells with TNF-alpha-stimulated mRNA expression and protein synthesis of M-CSF. Mesangial cell activation with PMA, a PKC activator, stimulated M-CSF mRNA expression while PKC depletion decreased M-CSF mRNA expression to control levels. Stimulation of PKC-depleted mesangial cells with either PMA or TNF-alpha inhibited M-CSF mRNA transcripts. Preincubation of mesangial cells with calphostin C, a PKC inhibitor, reduced both PMA- and TNF-alpha-induced M-CSF mRNA transcripts. Specific protein tyrosine kinase inhibitors blocked TNF-alpha-induced mesangial cell M-CSF mRNA expression. Additional studies showed that pertussis toxin, isoproterenol, and dibutyryl (db)cAMP did not induce mesangial cell M-CSF gene expression. However, coincubation of mesangial cells with TNF-alpha and either dbcAMP, forskolin, or pertussis toxin inhibited TNF-alpha-induced M-CSF gene expression. Finally, TNF-alpha-activated mesangial cell conditioned media stimulated monocyte/macrophage proliferation dose-dependently and was prevented by using anti-M-CSF. These data suggested that M-CSF can regulate monocyte differentiation into macrophages and proliferation within the mesangium induced by proinflammatory cytokines such as TNF-alpha. These cellular events appeared to be modulated by signal transduction pathways mediated by PKC and PTK.
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PMID:Activation of mesangial cells with TNF-alpha stimulates M-CSF gene expression and monocyte proliferation: evidence for involvement of protein kinase C and protein tyrosine kinase. 878 64

TNF-alpha has been implicated in glomerular cell activation to produce adhesion molecules and monocyte chemoattractants associated with glomerular monocyte infiltration. This study examined the regulatory role of protein kinases and cAMP on TNF-alpha-induced intercellular adhesion molecules-1 (ICAM-1) expression and monocyte adhesion to mesangial cells. Activation of mesangial cells with TNF-alpha induced ICAM-1 mRNA and protein expression. Mesangial cells preincubated with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, stimulated both the gene and protein expression of ICAM-1. Mesangial cell PKC depletion abolished ICAM-1 mRNA message, while activation with TNF-alpha did not inhibit ICAM-1 transcripts. Preincubation of mesangial cells with calphostin C did not affect TNF-alpha-induced mesangial cell ICAM-1 message, while it blocked PMA-induced ICAM-1 mRNA expression. Protein tyrosine kinase (PTK) inhibitors blocked TNF-alpha-mediated mesangial cell ICAM-1 transcripts. cAMP-generating substances (e.g., pertussis toxin, isoproterenol, or dibutyryl cAMP) did not induce mesangial cell ICAM-1 gene expression. However, incubation of mesangial cells with TNF-alpha and dibutyrl cAMP blocked TNF-alpha-induced ICAM-1 message. Finally, preincubation of mesangial cells with TNF-alpha increased monocyte adhesion that could be blocked by anti-ICAM-1. Parallel to ICAM-1 gene expression data, TNF-alpha-induced monocyte-mesangial cell adhesion was inhibited by PTK inhibitors, but was not regulated through either PKC or intracellular cAMP-associated pathways. These results suggest that increased ICAM-1 expression by TNF-alpha activation of mesangial cells is one of the major pathways involved in monocyte adhesion to the mesangium, a phenomenon presumably regulated by signal-transduction pathways dependent on PTK, but not PKC or cAMP.
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PMID:TNF-alpha stimulates monocyte adhesion to glomerular mesangial cells. The role of intercellular adhesion molecule-1 gene expression and protein kinases. 878 21

Monocyte chemotactic protein-1 (MCP-1), a specific chemoattractant for monocytes, has been thought to play an important role in the recruitment and accumulation of monocytes within the glomerulus seen in glomerular diseases. This study examined the role of tumor necrosis factor (TNF)-alpha-mediated cellular signal transduction pathways on mesangial cell MCP-1 gene expression and monocyte migration. Incubation of mesangial cells with TNF-alpha stimulated MCP-1 mRNA expression in a dose- and time-dependent manner. Phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, increased MCP-1 message by mesangial cells while depleting PKC decreased MCP-1 gene expression to control levels. Activation of PKC-depleted mesangial cells with PMA but not with TNF-alpha inhibited MCP-1 mRNA expression. Similarly, calphostin C, a PKC inhibitor, failed to inhibit TNF-alpha-induced MCP-1 expression. The incubation of mesangial cells with various protein tyrosine kinase inhibitors (PTK, e.g., herbimycin, tyrphostin, genistein) blocked TNF-alpha-induced MCP-1 mRNA message. Additional experiments examining the role of cAMP on MCP-1 expression indicated that the preincubation of mesangial cells with various cAMP generating substances (pertussis toxin, isoproterenol, dbcAMP) did not induce mesangial cell MCP-1 mRNA transcripts. However, the coincubation of mesangial cells with TNF-alpha and dbcAMP completely inhibited TNF-alpha-induced MCP-1 gene expression. Finally, TNF-alpha-activated mesangial cell media increased monocyte transmigration that could be blocked by neutralizing anti-MCP-1. These studies indicate that TNF-alpha facilitates monocyte transmigration into the glomerulus mediated by the increased expression of MCP-1 by mesangial cells. TNF-alpha-induced mesangial cell MCP-1 expression is regulated by signal transduction pathways involving PTK but not those dependent on PKC or cAMP.
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PMID:Role of tumor necrosis factor-alpha on mesangial cell MCP-1 expression and monocyte migration: mechanisms mediated by signal transduction. 879 1

The aim of this work was to study whether a G-protein regulates lipopolysaccharide (LPS) induced TNF-alpha production in tumour-bearing rat peritoneal macrophages differently to in normal rats. We also investigated whether a state of 'early endotoxin tolerance' affects LPS induced TNF-alpha release via a G-protein-mediated phenomenon. LPS-stimulated (50 micrograms ml-1 of Salmonella enteritidis LPS) TNF-alpha release was investigated in peritoneal macrophages harvested from both normal rats and tumour-bearing rats. Cholera toxin (10, 100 and 1000 ng ml-1) did not significantly modify LPS-induced TNF-alpha release. In contrast pertussis toxin (0.1, 1.0 and 10 ng ml-1) significantly increased LPS-induced TNF-alpha release and inhibited LPS-stimulated prostaglandin E2 (PGE2) production in both normal rat macrophages and tumour-bearing rat macrophages. Pertussis toxin effects on these LPS responses were correlated with a pertussis-toxin-mediated ADP-ribosylation of a 41 kDa protein(s). The LPS-mediated responses were significantly greater in macrophages from tumour-bearing rats than in macrophages from normal rats. PGE2 (10(-9), 10(-8) and 10(-7) M) suppressed LPS-induced TNF-alpha production in a dose-dependent fashion. A state of 'early endotoxin tolerance' was then induced in tumour-bearing rats by a single intravenous injection of 125 micrograms rat-1 of LPS, and experiments were performed on peritoneal macrophages harvested 24 h after LPS injection. In tolerant macrophages pertussis toxin induced an increase in LPS-stimulated TNF-alpha release and an inhibition in LPS-stimulated PGE2 release significantly lower than in macrophages harvested from non-tolerant tumour bearing rats. Our results suggest that a pertussis-toxin-sensitive G-protein may serve to regulate the synthesis of TNF-alpha in rat peritoneal macrophages and that the activity of this pertussis-sensitive G-protein is increased in macrophages from tumour-bearing rats. Furthermore, our experiments would indicate that a 'state of endotoxin tolerance', caused by altering the function of presumably a Gi-protein, may exert beneficial effects on the functions of macrophages in tumour-bearing rats.
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PMID:Endotoxin tolerance impairs a pertussis-toxin-sensitive G-protein regulating tumour necrosis factor release by macrophages from tumour-bearing rats. 888 Aug 92

Polymorphonuclear leukocyte-endothelial cell (PMN-EC) adhesion and the O2- production by subsequently triggered polymorphonuclear leukocytes (PMN) must be involved in the development of multiple organ failure at septic inflammatory sites. In this study, the adhesion and O2- production of PMN treated with LPS and serum, were markedly enhanced on the EC monolayer by treatment with TNF-alpha or LPS. However, in the intact EC monolayer, neither adhesion nor O2- production was increased. Monoclonal antibodies (mAb) against CD18, CD11b, and ICAM-1 inhibited PMN-EC adhesion. All antibodies except for anti-CD11b mAb had no effect on O2- production by adhered PMN. Anti-CD11b mAb stimulated O2- production in a PMN cell suspension. The pertussis toxin, an inhibitor of some G-proteins, inhibited this reaction. These findings indicate that the adhesion mediated by CD11b provides the signal for O2- production by PMN. This O2- production may involve a signal transduction mechanism mediated by pertussis toxin-sensitive G-proteins.
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PMID:Regulation of neutrophil O2- production by neutrophil-endothelial cell interaction via CD11b: its modulation by tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). 899 Jun 25

A simple procedure for elution in water of bacterial lipopolysaccharides (LPS) from sodium dodecyl sulfate-polyacrylamide gels is described. It consists of the combination of three principal steps: first, highly sensitive on-gel LPS detection (1-10 ng/band) with zinc-imidazole (negative or reverse staining); second, washing of the individual LPS band in a solution of a zinc-complexing agent (e.g., 100 mM EDTA); and finally, elution of the LPS (100-200 microliters water for a 0.5-microgram LPS band) from gel microparticles for 3 h at room temperature. Using this procedure, we have successfully eluted a variety of LPS forms from Bordetella pertussis, Escherichia coli 0111:B4, E. coli K-235, Salmonella enteritidis, and Pseudomonas aeruginosa. Elution recovery of rough or semismooth LPS was about 70-80%, while that of smooth LPS was only about 10%. Eluted LPS was biologically active as tested by limulus amebocyte lysate and TNF-alpha assays.
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PMID:Elution of lipopolysaccharides from polyacrylamide gels. 960 57

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