Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro formation and expansion of cysts derived from human renal cortex epithelial cells. 131 21

Preincubation of human peripheral blood polymorphonuclear leukocytes (HPPMN) with recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) enhanced the formylmethionyl-leucylphenylalanine (FMLP)-induced superoxide (O2-.) generation in a concentration- and preincubation time-dependent manner. The enhancement was very high for the FMLP- or opsonized zymosan (OZ)-induced O2-. generation, but was low for arachidonic acid (AA)- and phorbol myristate acetate (PMA)-induced O.2- generation. The rHuTNF-alpha has no effect on the steady state of intracellular calcium ion concentration ([Ca2+]i) nor on the membrane potential of neutrophils. The rHuTNF-alpha-primed FMLP-induced O2-. generation was inhibited by nicotineamide (NA), pertussis toxin (PT), and by the tyrosine kinase (TK) inhibitor, genistein, but was enhanced by the protein kinase C (PKC) inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-3-methyl-piperazine). The inhibitory actions of NA and PT were also observed in in vivo primed guinea pig peritoneal neutrophils (GPtPMN). However, FMLP-induced O2-. generation of GPtPMN was enhanced by genistein, but was inhibited by H-7. These data indicate that TNF-alpha does not induce changes in [Ca2+]i nor in membrane potential of HPPMN, and that TNF-alpha-primed FMLP-induced O.2- generation of HPPMN is coupled with ADP-ribosylation and activation of G-proteins, and that protein kinases, especially TK, seem to exert an important role in the priming action of TNF.
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PMID:Effect of tumor necrosis factor-alpha on the stimulus-coupled responses of neutrophils and their modulation by various inhibitors. 132 5

Transmembrane signalling mechanisms of tumor necrosis factor alpha (TNF alpha) were examined with special reference to the involvement of G-protein, in intact and permeabilized murine osteoblast-like cells. TNF alpha stimulated the release of 3H radioactivity from intact cells labeled with [3H]arachidonic acid within 10 min in a dose dependent manner and the production of lyso forms of phospholipids, an event presumably mediated through the activation of phospholipase A2. Production of cAMP and inositol 1,4,5-trisphosphate was not affected by TNF alpha. Pretreatment of the cells with pertussis toxin inhibited the liberation of [3H]arachidonate. GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) reduced the binding affinity of [125I]TNF alpha to beta-escin-permeabilized cells. The addition of TNF alpha together with an unhydrolyzable analog of GTP, GTP gamma S, to the beta-escin-permeabilized cells prelabeled with [3H]arachidonic acid led to a release of the 3H radioactivity. The production of prostaglandin E2 (PGE2) was markedly stimulated by TNF alpha in a dose over 100 ng/ml, with a latent time of about 3 h, and the stimulation was abolished by pretreatment with pertussis toxin. The time and dose requirements for this process differed from those for the possible activation of phospholipase A2, thereby indicating that other process(es) in addition to the activation of phospholipase A2 may be responsible for the enhanced production of PGE2. The activity of cyclooxygenase (i.e. the combined activities of prostaglandin endoperoxide syntase and PGH2-PGE2 isomerase) was stimulated by TNF alpha with much the same time and dose requirements as for the production of PGE2, and the activation was found to be due to the increased amount of the enzyme, as assessed by a Western blot analysis with anti-cyclooxygenase antibody. This process was also sensitive to pertussis toxin. Therefore, receptors for TNF alpha in MC3T3-E1 cells apparently couple to G-protein sensitive to pertussis toxin and the coupling regulates the activations of phospholipase A2 and the de novo synthesis of cyclooxygenase.
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PMID:Signal transduction by tumor necrosis factor alpha is mediated through a guanine nucleotide-binding protein in osteoblast-like cell line, MC3T3-E1. 137 94

Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H-arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A.
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PMID:Cytokine regulation of adenylate cyclase activity in LLC-PK1 cells. 140 34

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
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PMID:BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. 141 7

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified and examined for relief of morphine dependence by observing its inhibition of the jumping of mice on naloxone-precipitate withdrawal. Administration of LPSp either intravenously or intradermally showed marked inhibition of the jumping. Beta-endorphin in mouse serum and brain tissue were recognized to be in synchrony with the time course of the relief. Administration of TNF-alpha gave similar effect, suggesting that LPSp induces a cytokine cascade to produce endogenous TNF followed by ACTH/beta-LPH gene products and beta-endorphin. The effect of LPSp was better than that of LPS from E. coli or Bordetella pertussis, and thus is considered to be applicable for clinical use.
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PMID:Inhibition of morphine dependence by a lipopolysaccharide from Pantoea agglomerans. 142 Oct 14

This review outlines evidence that IL-1, IL-2, and TNFs modulate neutrophil functions. These cytokines affect some or all of the following functions of the neutrophil: adherence, cell migration, respiratory burst, lysosomal enzyme release, and cell surface receptor expression. TNFs, especially TNF alpha, remains one of the most highly studied cytokine with respect to regulation of neutrophil function. TNFs are a direct stimuli for the neutrophil respiratory burst and weak stimuli of lysosomal enzyme release. The cytokines enhance cell adhesion and inhibit neutrophil migration. The TNFs augment the oxidative burst and lysosomal enzyme release response to a wide range of soluble and particulate cell stimuli. These changes in the cell seem to be closely correlated with the increased fungicidal, bactericidal, tumoricidal, and protozoacidal activity of the TNF-primed neutrophils. In contrast to TNFs, IL-1 and IL-2 inhibit neutrophil adherence, and this provides evidence that the cytokine family represents a regulatory system. Another form of regulation of TNF alpha and IL-1 neutrophil-activating activity is by the release of inhibitors to these cytokines (58). We have evidence which shows that the soluble TNF alpha inhibitor (a cleaved product of the TNF alpha receptor) (59) binds and inhibits TNF from activating and priming neutrophils (60). Priming of neutrophils by TNFs involves surface receptor binding but is independent of protein kinase C system, pertussis toxin-sensitive guanine nucleotide regulatory protein, and direct burst of respiratory activity. The translocation of cell surface receptors and constituents of the NADPH oxidase from stored vesicles may be the major mechanism of TNF-induced cell priming.
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PMID:Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. 150 43

Treatment of cultured rat cardiomyocytes in serum-free medium for 48 h with recombinant human tumor necrosis factor alpha (TNF alpha) led to a concentration-dependent increase in the level of membrane-inhibitory guanine nucleotide-binding protein (Gi) alpha-subunits and in pertussis toxin-catalyzed [32P]ADP ribosylation of 40 kDa proteins. Both Gi alpha protein subtypes present in rat cardiac myocyte membranes, Gi alpha 40 and Gi alpha 41, were up-regulated by the cytokine, with the maximal increase occurring at 10 U/ml TNF alpha. In contrast to noradrenaline exposure, which causes a similar, but apparently exclusive, increase in alpha i-subunits, treatment with TNF alpha in addition increased the level of membrane G protein beta 36-subunits. Furthermore, while noradrenaline exposure led to a decrease in receptor-dependent and -independent adenylyl cyclase activity, treatment of cardiomyocytes with TNF alpha caused a concentration-dependent increase in cyclase responsiveness to either forskolin, guanosine 5'-O-(3-thiotriphosphate) or isoproterenol, even though beta-adrenoceptor density was decreased by TNF alpha. The increase in adenylyl cyclase activity induced by TNF alpha was completely suppressed when the cells were cocultured with noradrenaline, a condition leading to an additive increase in Gi alpha level. The data indicate that the cytokine TNF alpha can potently modulate G protein-mediated signal transduction in rat cardiac myocytes. Although TNF alpha, like noradrenaline, exposure of the cells increased the level of membrane Gi alpha proteins, it did not decrease but rather caused an increase in adenylyl cyclase responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor alpha up-regulates Gi alpha and G beta proteins and adenylyl cyclase responsiveness in rat cardiomyocytes. 164 97

The effects of pertussis toxin (PT) on the growth and dimethylsulfoxide (Me2SO4)-induced differentiation of the HL-60 human promyelocytic leukemia cell line were tested. Cell growth was quantified by direct cell counts. Cell differentiation was estimated by measuring the expression of myeloid-specific cell-surface antigens (Mo-1 and fMet-Leu-Phe [fMLP] receptors), the ability of the cells to produce superoxide anions on stimulation with fMLP, the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA), and by monitoring the level of expression of messenger RNA (mRNA) for tumor necrosis factor alpha (TNF alpha). By itself, PT did not affect the proliferation of HL-60 cells in serum-containing medium. In contrast, PT (but not its B-oligomer) dose-dependently inhibited the Me2SO4-induced expression of Mo-1, fMLP receptors, and the oxidative responses to the chemotactic factor and to A23187, but not to PMA. The addition of Me2SO4 induced a significant increase in the steady-state levels of TNF alpha mRNA, and this effect was strongly inhibited by PT. Finally, the bacterial toxin did not reverse the block of cell division that follows the addition of Me2SO4. These results provide evidence for the involvement of a PT substrate (presumably a guanine nucleotide-binding protein) in the regulation of the maturation of the excitation-response coupling sequence in human myeloid cell precursors and show that the regulation of cell division and maturation of HL-60 cells are under distinct sets of control mechanisms.
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PMID:Pertussis toxin selectively interferes with the responses of the HL-60 human promyelocytic cell line to dimethylsulfoxide. 182 51

Monocyte-derived neutrophil chemotactic factor (MDNCF)/IL-8, a novel cytokine, distinct from IL-1 and TNF was recently purified and cloned. This study was performed to investigate the biologic effect of recombinant MDNCF/IL-8 on human polymorphonuclear neutrophils (PMN) by assessment of their growth inhibitory activity against Candida albicans. The chemoattractant, FMLP was used as a positive control. We demonstrated that MDNCF/IL-8, similar to FMLP, effectively enhanced PMN-mediated anti-Candida activity. MDNCF/IL-8, from 1.0 to 1000 ng/mol, enhanced PMN-mediated anti-Candida activity, whereas FMLP was effective from 10(-10) to 10(-7) M. The optimal dose of MDNCF/IL-8 for PMN stimulation was 10 ng/ml which equalled the optimal chemoattractant dose. MDNCF/IL-8 itself, like FMLP, had no direct effect on Candida growth at any concentration and it stimulated antifungal activity only in PMN but not in monocytes. Interestingly, MDNCF/IL-8 failed to stimulate directly the production of superoxide from PMN or prime the respiratory burst of PMN exposed to FMLP. However, MDNCF/IL-8 was capable of releasing azurophilic enzymes from cytochalasin B-treated PMN into the extracellular space. Enhancement of PMN anti-Candida activity and release of azurophilic enzymes from PMN by MDNCF/IL-8 were inhibited in the presence of colchicine, which is a known inhibitor of degranulation. These results suggest that MDNCF/IL-8 induced antifungal action of PMN via oxygen-independent pathways. Furthermore, MDNCF/IL-8 induction of anti-Candida action by PMN was inhibited by pretreatment with Bordetella pertussis toxin, suggesting that enhancement of PMN antifungal activity by MDNCF/IL-8, as well as by FMLP, may be mediated by a GTP-binding protein.
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PMID:Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. 215 63


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