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)

Macrophage colony-stimulating factor (M-CSF) is required for the proliferation, differentiation, and activation of monocytes. High-affinity receptors for M-CSF are encoded by the c-fms proto-oncogene. In the present study, we show that c-fms transcripts are detectable in human THP-1 myeloid leukemia cells. Furthermore, radiolabeled 125I-M-CSF is rapidly internalized into THP-1 cells and then degraded intracellularly. The results also show that treatment of THP-1 cells with M-CSF is associated with the activation of protein kinase C (PKC) and the induction of tumor necrosis factor (TNF) gene expression. TNF transcript levels were low to undetectable in uninduced THP-1 cells, reached maximal levels by 1 hour of exposure to M-CSF, and returned to those of control cells by 24 hours. Transcriptional run-on analysis showed that a low level of TNF transcription is detectable in untreated THP-1 cells, and M-CSF treatment increased the rate of TNF transcription. Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF. Moreover, exposure of THP-1 cells to inhibitors of protein kinase activity blocked the increase in TNF messenger RNA. These findings suggest that at least two M-CSF-mediated signaling pathways exist in THP-1 cells and that the induction of TNF may be regulated by a protein kinase-dependent mechanism distinct from PKC.
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PMID:Functional expression of the macrophage colony-stimulating factor receptor in human THP-1 monocytic leukemia cells. 153 7

Leukemic cell growth in the marrow microenvironment may be modulated by stromal cell products, including stimulatory growth factors and the inhibitory regulator prostaglandin E. The production of both of these stromal cell products induced by cytokine mediators appears to be closely linked. Cyclic AMP (cAMP) is an intracellular second messenger that inhibits myeloid cell proliferation and is produced in myeloid leukemia cells on stimulation of adenylate cyclase enzyme by prostaglandin E1 (PGE1). Cells expressing the product of an RAS oncogene have been observed to display diminished hormone-stimulated adenylate cyclase of membranes. If this observation were applicable to myeloid cells, a potentially important mode for leukemia cells expressing p21 RAS to escape inhibitory regulation within the hematopoietic microenvironment would be identified. We studied an interleukin-3 (IL-3)-dependent myeloid cell line, NFS/N1.H7, and a derivative line transfected with H-RAS codon 12 (T24) oncogene, H7 Neo Ras.F3, for inhibition of proliferation by PGE1, 1 microM, alone or in combination with pertussis toxin, which inactivates Gi, an inhibitory regulatory guanosine triphosphate (GTP)-binding protein of adenylate cyclase. NFS/N1.H7 cells were inhibited in interleukin-3-dependent proliferation (dose range, IL-3 10 to 100 U/mL) by PGE1 79 +/- 11%, by pertussis toxin 51 +/- 9%, and by the combination 92 +/- 2%, whereas H7 Neo RAS.F3 was inhibited 51 +/- 7%, 6 +/- 2%, or 58 +/- 9% by PGE1, pertussis toxin, and the combination, respectively. These differences in capacity for inhibition by adenylate cyclase agonists between RAS-transfectant cells (lower inhibition) versus parent cells (greater inhibition) were all highly significant (P less than .0005). Intracellular cAMP formed on PGE1 stimulation of pertussis-intoxicated cells was 150% lower in RAS-transfectant cells than in parent cells. The adenylate cyclase activity of membranes from pertussis-intoxicated RAS-transfected cells was 1.5 to two times lower than that of pertussis-intoxicated parent-cell membranes on Mg2+-dependent activation by hormone and/or guanine nucleotide. However, very similar adenylate cyclase activity was observed in oncogenic p21 RAS-containing membranes compared with parental membranes under conditions of direct activation by 4 mM Mn2+ and forskolin, where inhibitory or stimulatory G-protein influences are minimal. These studies showed diminished adenylate cyclase activity in mutant RAS-bearing myeloid-cell membranes compared with parent-cell membranes independent of the pertussis toxin-sensitive G protein, Gi.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effector function for RAS oncogene in interleukin-3-dependent myeloid cells involves diminished efficacy of prostaglandin E1-mediated inhibition of proliferation. 267 12

The migration of leukocytes into tissues is regulated by chemokines and other chemotactic factors that act on receptors that signal through Gi proteins. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. In fact, dissemination of a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic subunit of pertussis toxin that had been transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma cells, but it did not prevent bone marrow colonization. In contrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemination to the liver and spleen. This indicates that the influx of these myeloid cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. (Blood. 2000;96:691-698)
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PMID:Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi. 1088 36

The neuropeptides Vasoactive-intestinal peptide (VIP) and Pituitary adenylate-cyclase activating protein (PACAP) increased cAMP levels in three out of five human myeloid leukemic cell lines tested while an increased in calcium intracytoplasmic levels was seen only in one cell line (HEL). This increase was phospholipase C, Pertussis toxin dependent and associated with an increase in c-fos and c-jun protein expression together with the formation of functional AP-1 transcriptional factor complex. Cell exposure to VIP or PACAP resulted in a decrease in HEL cell proliferation associated with a down-regulation of the erythroid marker, Glycophorin A. Both peptides were found to increase intra-cytoplasmic calcium levels in blasts isolated from patients with myeloid leukemia. Thus VIP and PACAP are involved in the physiology and pathophysiology of human myeloid cells.
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PMID:The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) modulate several biochemical pathways in human leukemic myeloid cells. 1502 77

N-formyl-methionyl-leucyl-phenylalanine (fMLP) is a major chemotactic factor produced by Escherichia coli and other Gram-negative bacteria. The prototypal human fMLP receptor 1 (FPR1) was cloned in 1990 from a differentiated HL-60 myeloid leukemia cell cDNA library. In transfected cells, FPR1 binds fMLP with high affinity and is activated by picomolar to low nanomolar concentrations of fMLP in chemotaxis and calcium ion mobilization assays. Two additional human genes, designated FPR-like 1 (FPRL1) and FPR-like 2 (FPRL2), were later isolated by low-stringency hybridization using FPR1 cDNA as a probe, and these were shown to cluster with FPR1 on chromosome 19q13.3. In avian models the fMLP effects and the possible expression of FPRs have been poorly investigated. In this study we demonstrated that stimulation with fMLP of cultured cells isolated from the 10-day chick embryo brain causes superoxide anion and nitric oxide release and protein phosphorylation at serine, threonine, and tyrosine residues. These effects were abrogated by pretreatment with pertussis toxin, suggesting the involvement of a G-protein-coupled receptor (GPCR). Although specific N-formyl peptide receptors have so far been demonstrated only in mammals, a specific polyclonal antihuman-FPR1 antibody proved to bind to the membrane of both neurons and glial cells isolated from the chick brain. Immunoblot analysis revealed a single band corresponding to 60 kDa ca. A BLAST search and aa sequence alignments demonstrated that a number of avian 7-transmembrane (7TM) GPCRs share some homologies with the human FPR1. Furthermore, the CXCR4 ligand, SDF-1alpha, seems to compete with the antihuman-FPR1 polyclonal antibody used in our experiments. We thus advance the hypothesis that in birds one (or more) of the expressed 7TM GPCRs, most probably chemokine receptors belonging to the CXCR4 subfamily, also may act as fMLP receptors.
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PMID:Formyl peptide receptor expression in birds. 1746 63

Eight G protein-coupled receptors comprise the P2Y receptor family of cell signaling proteins. The goal of the current study was to define native cell signaling pathways regulated by the uridine nucleotide sugar-activated P2Y(14) receptor (P2Y(14)-R). The P2Y(14)-R was stably expressed in human embryonic kidney (HEK) 293 and C6 rat glioma cells by retroviral infection. Nucleotide sugar-dependent P2Y(14)-R activation was examined by measuring inhibition of forskolin-stimulated cAMP accumulation. The effect of P2Y(14)-R activation on mitogen-activated protein kinase signaling also was studied in P2Y(14)-HEK293 cells and in differentiated HL-60 human myeloid leukemia cells. UDP-Glc, UDP-galactose, UDP-glucuronic acid, and UDP-N-acetylglucosamine promoted inhibition of forskolin-stimulated cAMP accumulation in P2Y(14)-HEK293 and P2Y(14)-C6 cells, and this signaling effect was abolished by pretreatment of cells with pertussis toxin. Inhibition of cAMP formation by nucleotide sugars also was observed in direct assays of adenylyl cyclase activity in membranes prepared from P2Y(14)-C6 cells. UDP-Glc promoted concentration-dependent and pertussis toxin-sensitive extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in P2Y(14)-HEK293 cells. P2Y(14)-R mRNA was not observed in wild-type HL-60 cells but was readily detected in dimethyl sulfoxide-differentiated cells. Consistent with this observation, no effect of UDP-Glc was observed in wild-type HL-60 cells, but UDP-Glc-promoted pertussis toxin-sensitive activation of ERK1/2 occurred after differentiation. These results illustrate that the human P2Y(14)-R signals through G(i) to inhibit adenylyl cyclase, and P2Y(14)-R activation also leads to ERK1/2 activation. This work also identifies two stable P2Y(14)-R-expressing cell lines and differentiated HL-60 cells as model systems for the study of P2Y(14)-R-dependent signal transduction.
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PMID:Gi-dependent cell signaling responses of the human P2Y14 receptor in model cell systems. 1933 61