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

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

Phorbol esters induce the differentiation of the human promonocytic cell line U937 to a monocyte/macrophage. This process is associated with the induction of interleukin 1 beta (IL-1 beta) gene expression (Strulovici, B., Daniel-Issakani, S., Oto, E., Nestor, J., Jr., Chan, H., and Ping-Tsou, A. (1989) Biochemistry 28, 3569-3576). Here we describe the induction by phorbol esters of lipopolysaccharide (LPS) responsiveness in U937 cells. Preincubation with phorbol myristate acetate (TPA, 5 x 10(-8) M) for at least 4-6 h and up to 12 h followed by 3 h of LPS treatment induced a 4-fold enhancement in the accumulation of IL-1 beta transcripts compared to treatment with TPA alone. This "priming" effect was specific for protein kinase C agonists and required de novo protein synthesis. Exposure of [35S]methionine-labeled U937 cells to phorbol esters induced the de novo synthesis of a protein which migrated with a 40-kDa molecular mass in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, had an isoelectric point of 5.7 (p 40/5.7), and was recognized by a specific antibody to the pertussis toxin (PT)-sensitive Gi2. The time course for the appearance of Gi2 correlated with that for the induction of LPS responsiveness by TPA. Moreover, the LPS response was PT-sensitive. In cells treated with LPS for 5 min, Gi2 showed diminished ADP-ribosylation by PT. Treatment of U937 cells with LPS for 30 min induced phosphorylation of Gi2 and enhanced PT labeling. In a cell-free assay, phosphorylation of Gi2 by protein kinase C type III, rendered it a better PT substrate. The present findings thus suggest: 1) that TPA induces LPS responsiveness in U937 cells via de novo synthesis of Gi2; 2) that the LPS response (enhanced IL-1 production) is linked to a pertussis toxin-sensitive G protein which we identified as Gi2; and 3) that LPS leads to phosphorylation of Gi2.
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PMID:Lipopolysaccharide response is linked to the GTP binding protein, Gi2, in the promonocytic cell line U937. 251 Dec

The guanine nucleotide regulatory proteins (G-proteins) which are substrates for ADP-ribosylation by pertussis toxin (alpha i-1, alpha i-2, alpha i-3 and alpha o) transduce a variety of hormonal signals. Endothelial cells express mRNA for three alpha i subtypes although the level of alpha i-1 mRNA is very low. Interleukin 1 beta (IL 1 beta), a pleiotropic inflammatory mediator which stimulates a complex series of responses in human endothelial cells leading to increased coagulation and platelet adhesion, increases expression of one subtype of alpha i (alpha i-2) mRNA in human endothelial cells as determined by Northern blot analysis without affecting the level of mRNA for other alpha-subunits. These studies show that mRNA levels for alpha i subtypes are independently regulated, suggesting that there may be subtype specificity in the cell's requirements for the Gi class of signal-transducing proteins.
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PMID:Subtype-specific increase in G-protein alpha-subunit mRNA by interleukin 1 beta. 252 85

Inflammation removes developing and mature lymphocytes from the bone marrow (BM) and induces the appearance of developing B cells in the spleen. BM granulocyte numbers increase after lymphocyte reductions to support a reactive granulocytosis. Here, we demonstrate that inflammation, acting primarily through tumor necrosis factor alpha (TNFalpha), mobilizes BM lymphocytes. Mobilization reflects a reduced CXCL12 message and protein in BM and changes to the BM environment that prevents homing by cells from naive donors. The effects of TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily to expand the BM granulocyte compartment. Our observations indicate that inflammation induces lymphocyte mobilization by suppressing CXCL12 retention signals in BM, which, in turn, increases the ability of IL-1beta to expand the BM granulocyte compartment. Consistent with this idea, lymphocyte mobilization and a modest expansion of BM granulocyte numbers follow injections of pertussis toxin. We propose that TNFalpha and IL-1beta transiently specialize the BM to support acute granulocytic responses and consequently promote extramedullary lymphopoiesis.
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PMID:Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. 1470 14

The present study was designed to investigate the mechanisms involved in the antinociception afforded by myricitrin in chemical models of nociception in mice. Myricitrin given by intrathecal (i.t.) or intracerebroventricular (i.c.v.) route produced dose-related antinociception when evaluated against acetic acid-induced visceral pain in mice. In addition, the intraperitoneal administration of myricitrin caused significant inhibition of biting behaviour induced by i.t. injection of glutamate, substance P, capsaicin, interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). The antinociception caused by myricitrin in the acetic acid test was fully prevented by i.t. pre-treatment with pertussis toxin, a Gi/o protein inactivator, and by i.c.v. injection of calcium chloride (CaCl(2)). In addition, the i.t. pre-treatment of mice with apamin, a blocker of small (or low)-conductance calcium-gated K(+) channels and tetraethylammonium, a blocker of voltage-gated K(+) channels significantly reversed the antinociception induced by myricitrin. The charybdotoxin, a blocker of large (or fast)-conductance calcium-gated K(+) channels and glibenclamide, a blocker of the ATP-gated K(+) channels had no effect on myricitrin-induced antinociception. Calcium uptake analysis revealed that myricitrin inhibited (45)Ca(2+) influx under a K(+)-induced depolarization condition. However, calcium movement was modified in a non-depolarizing condition only when the highest concentration of myricitrin was used. In summary, our findings indicate that myricitrin produces consistent antinociception in chemical models of nociception in mice. These results clearly demonstrate an involvement of the Gi/o protein dependent mechanism on antinociception caused by myricitrin. The opening of voltage- and small-conductance calcium-gated K(+) channels and the reduction of calcium influx led to the antinociceptive of myricitrin.
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PMID:Antinociceptive action of myricitrin: involvement of the K+ and Ca2+ channels. 1746 89