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)

Many membrane proteins are implicated in the control of cell function by triggering specific signaling pathways. There is a new family of membrane proteins, defined by its structural motifs, which includes several lymphoid antigens, but lacks a function. To study its biological role, we determined which signaling pathways are affected by the CD53 antigen, a prototypic member of this family, in rat macrophages. Activation of CD53 by cross-linking results in an increase in inositol phosphates and diacylglycerol and in Ca2+ mobilization, which are insensitive to pertussis or cholera toxins. There is a translocation of protein kinase C to the membrane accompanied by nitric oxide (NO) release in macrophages. This effect is the result of the expression of the inducible nitric oxide synthase (iNOS), which is dependent on protein kinase C and protein synthesis. These results have linked a new receptor with a specific pathway of NO induction and thus have opened up a novel aspect of NO regulation in cell biology.
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PMID:Induction of nitric oxide release by MRC OX-44 (anti-CD53) through a protein kinase C-dependent pathway in rat macrophages. 751 80

Administration of whole-cell diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) caused marked depression in the expression of mRNA for isozymes of cytochrome P-450 in the livers of endotoxin-responsive and nonresponsive mice. The levels of expression of mRNA for a polycyclic aromatic hydrocarbon-inducible (CYP1A2) and an ethanol-inducible (CYP2E1) form of P-450 were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis endotoxin administration. These effects are preceded by marked increases (threefold to sixfold) in mRNA expression for interleukin-6, interleukin-1 and tumor necrosis factor in both strains of mice, with maximal increases 1 to 2 hr after injection. This is the first demonstration that levels of cytokine mRNA are altered in the liver in response to DTP vaccine administration. The finding of increased cytokine mRNA in the livers of mice injected with vaccine supports a role for cytokines as mediators of the decreased levels of cytochrome P-450. In addition, inducible nitric oxide synthase mRNA expression is also increased after vaccine administration, with a peak at 4 hr. The temporal relationship of the increased cytokine mRNA expression, increased nitric oxide synthase and decreased expression of P-450 mRNAs suggests a mechanism by which cytokines mediate the induction of nitric oxide synthase, which increases nitric oxide and decreases the activities of some cytochromes P-450.
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PMID:Modulation of hepatic mRNA levels after administration of lipopolysaccharide and diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) to mice. 752 68

We have investigated the synergistic interactions of a naturally occurring peptidoglycan fragment (muramyl peptide) and bacterial endotoxin in the induction of inflammatory processes within respiratory epithelial cells, at the levels of both signal transduction events and ultimate cellular metabolic effects. The source of the muramyl peptide is Bordetella pertussis, the causative agent of the respiratory disease pertussis. During log-phase growth, B. pertussis releases the muramyl peptide tracheal cytotoxin (TCT), which has the structure N - acetylglucosaminyl - 1,6 - anhydro - N - acetylmuramyl - (L) - alanyl - gamma - (D) - glutamyl - meso - diaminopimelyl - (D) - alanine, equivalent to a monomeric subunit of gram-negative bacterial peptidoglycan. When applied to hamster trachea epithelial (HTE) cells, TCT and endotoxin were found to be highly synergistic in the induction of interleukin-1alpha (IL-1alpha), type II (inducible) nitric oxide synthase (iNOS), nitric oxide production, and inhibition of DNA synthesis. Neither molecule alone significantly triggered these responses. The serine/threonine protein kinase inhibitor H7 blocked induction of both IL-1alpha and iNOS. More selective inhibitors of protein kinase C, cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase were not capable of blocking the effects of TCT and endotoxin, suggesting that the H7-inhibited component in this pathway is not among the commonly described kinase targets of H7. Treatment of HTE cells with exogenous IL-1 reproduced the induction of iNOS and DNA synthesis inhibition caused by TCT and endotoxin. H7 was not capable of interfering with effects caused by exogenous IL-1, implying that the H7-sensitive step in the pathway is upstream of IL-1 protein production. Similar assays with the phorbol ester phorbol myristate acetate indicate that it could effectively synergize with endotoxin but not with TCT, suggesting that TCT and endotoxin induce different signal transduction events that combine synergistically. The synergy observed with TCT and endotoxin in epithelial cells is significantly different from their interaction with other cell types, revealing a unique inflammatory response by epithelial cells to these natural bacterial products.
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PMID:Synergistic epithelial responses to endotoxin and a naturally occurring muramyl peptide. 1067 32

The involvement of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha), which have diverse roles in the progression of autoimmune disease models, was studied in pertussis toxin (PT)-induced hyperacute experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The expression of TNF-alpha mRNA (increased 5-fold, P<0.01) and iNOS protein (3-fold, P<0.01) was much greater in the spinal cords with PT(+) EAE at the peak stage of EAE than in those with PT(-) EAE, as shown by competitive PCR and Western blot analysis, respectively. Immunohistochemistry showed that the majority of ED1-positive macrophages in EAE lesions contained iNOS, and that there were many more iNOS-positive cells in the CNS lesions of PT(+) rats than in those of PT(-) rats. These findings suggest that PT-induced hyperacute EAE is partly mediated by the enhanced expression of iNOS and TNF-alpha in the early stages of rat EAE.
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PMID:Pertussis toxin-induced hyperacute autoimmune encephalomyelitis in Lewis rats is correlated with increased expression of inducible nitric oxide synthase and tumor necrosis factor alpha. 1144 81

The mechanism whereby whole-cell pertussis vaccines (WCV) confer protection against Bordetella pertussis is still not fully understood. We have previously reported that macrophage activation produced by vaccination with WCV is associated with induction of NO synthesis by macrophages in response to in vitro stimulation with B. pertussis antigens. To determine whether NO production is an effector of protection or simply a marker of activation, the susceptibility of inducible nitric oxide synthase (type II, iNOS) knockout mice to infection with B. pertussis was examined. We showed that iNOS knockout mice were more susceptible to B. pertussis respiratory challenge than wild-type mice. iNOS-deficient mice also developed a less effective protective response than wild-type mice after the same immunization with WCV. This suggests that NO plays an important role in effecting protection against B. pertussis challenge.
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PMID:Investigation of role of nitric oxide in protection from Bordetella pertussis respiratory challenge. 1179 99

Bacterial N-formyl peptides such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) are important mediators of monocyte/macrophage recruitment and activation at the sites of inflammation. In the current study, the role of nitric oxide (NO) in the activation of murine peritoneal macrophages to tumoricidal state in response to in vitro fMLP treatment has been investigated. Murine peritoneal macrophages on treatment with fMLP showed a dose- and time-dependent production of NO together with increased tumoricidal activity against P815 mastocytoma cells. L-NMMA, a specific inhibitor of L-arginine pathway, inhibited the fMLP-induced NO secretion and macrophage-mediated tumoricidal activity against P815 cells. These results indicate the L-arginine-dependent production of NO to be one of the effector mechanisms contributing to the tumoricidal activity of fMLP-treated macrophages. The expression of iNOS protein and iNOS mRNA is also observed. The pharmacological inhibitors genistein, wortmannin, H7, PD98059, TPCK, and pertussis toxin (PTX) blocked the fMLP-induced NO production, suggesting the involvement of tyrosine kinases, PI3K, PKC, p42/44 MAPkinase, NF-kappa B, and G-proteins. The expression of phospho-p42/44 MAPK and phospho-I kappa B was also observed. The role of protein phosphatases in the above pathway has been suggested using the specific inhibitors of these phosphatases, i.e., okadaic acid and sodium orthovanadate.
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PMID:fMLP-induced in vitro nitric oxide production and its regulation in murine peritoneal macrophages. 1181 47

It has been postulated that intracellular binding sites for platelet-activating factor (PAF) contribute to proinflammatory responses to PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCECs) produced PAF-molecular species in response to H(2)O(2). Using FACS analysis, we demonstrated the expression of PAF receptors on cell and nuclear surfaces of PCECs. Confocal microscopy studies performed on PCECs, Chinese hamster ovary cells stably overexpressing PAF receptors, and isolated nuclei from PCECs also showed a robust nuclear distribution of PAF receptors. Presence of PAF receptors at the cell nucleus was further revealed in brain endothelial cells by radioligand binding experiments, immunoblotting, and in situ in brain by immunoelectron microscopy. Stimulation of nuclei with methylcarbamate-PAF evoked a decrease in cAMP production and a pertussis toxin-sensitive rise in nuclear calcium, unlike observations in plasma membrane, which exhibited a pertussis toxin-insensitive elevation in inositol phosphates. Moreover, on isolated nuclei methylcarbamate-PAF evoked the expression of proinflammatory genes inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) and was associated with augmented extracellular signal-regulated kinase 1/2 phosphorylation and NF-kappaB binding to the DNA consensus sequence. COX-2 expression was prevented by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 and NF-kappaB inhibitors. This study describes for the first time the nucleus as a putative organelle capable of generating PAF and expresses its receptor, which upon stimulation induces the expression of the proinflammatory gene COX-2.
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PMID:Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. 1244 57

Lysophosphatidic acid (LPA) is a bioactive molecule involved in inflammation, immunity, wound healing, and neoplasia. Its pleiotropic actions arise presumably by interaction with their cell surface G protein-coupled receptors. Herein, the presence of the specific nuclear lysophosphatidic acid receptor-1 (LPA1R) was revealed in unstimulated porcine cerebral microvascular endothelial cells (pCMVECs), LPA1R stably transfected HTC4 rat hepatoma cells, and rat liver tissue using complementary approaches, including radioligand binding experiments, electron- and cryomicroscopy, cell fractionation, and immunoblotting with three distinct antibodies. Coimmunoprecipitation studies in enriched plasmalemmal fractions of unstimulated pCMVEC showed that LPA1Rs are dually sequestrated in caveolin-1 and clathrin subcompartments, whereas in nuclear fractions LPA1R appeared primarily in caveolae. Immunofluorescent assays using a cell-free isolated nuclear system confirmed LPA1R and caveolin-1 co-localization. In pCMVEC, LPA-stimulated increases in cyclooxygenase-2 and inducible nitric-oxide synthase RNA and protein expression were insensitive to caveolea-disrupting agents but sensitive to LPA-generating phospholipase A2 enzyme and tyrosine kinase inhibitors. Moreover, LPA-induced increases in Ca2+ transients and/or iNOS expression in highly purified rat liver nuclei were prevented by pertussis toxin, phosphoinositide 3-kinase/Akt inhibitor wortmannin and Ca2+ chelator and channel blockers EGTA and SK&F96365, respectively. This study describes for the first time the nucleus as a potential organelle for LPA intracrine signaling in the regulation of pro-inflammatory gene expression.
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PMID:Modulation of pro-inflammatory gene expression by nuclear lysophosphatidic acid receptor type-1. 1284 11

In the present study, we report the activation of murine peritoneal macrophages in vitro on irradiation with sublethal dose of UVB (50 mJ/cm(2)). The activation involves enhanced expression of CD18 molecule and production of nitric oxide (NO), tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1). Production of NO, TNF-alpha and IL-1 by the macrophages on UVB irradiation was found to peak at 24 h of incubation post UVB irradiation. Increased iNOS, TNF-alpha and IL-1beta mRNAs expression was also observed by reverse transcription and polymerase chain reaction (RT-PCR). The RT-PCR results also showed the increased transcription of IL-6, IL-12, TLR2 and TLR4 genes in UVB-irradiated macrophages. Increased expression of phospho-IkappaB was also observed by immunoblotting in UVB-irradiated macrophages. Investigating the signal transduction pathway responsible for the NO, TNF-alpha and IL-1 production by the UVB-irradiated macrophages, it was observed that the pharmacological inhibitors pertussis toxin, wortmannin, PD98059, SB202190 and genistein blocked NO, TNF-alpha and IL-1 production suggesting the probable involvement of G-proteins, phosphoinositol-3-kinase, p42/44, p38 mitogen activated protein kinases and tyrosine kinases in the above process.
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PMID:In vitro activation of murine peritoneal macrophages by ultraviolet B radiation: upregulation of CD18, production of NO, proinflammatory cytokines and a signal transduction pathway. 1507 50

The present study describes a new model of autoimmune neuritis in C57BL/6 mice induced by immunization with the novel neuritogenic epitope P0(106-125), derived from mouse peripheral myelin protein P0. Immunization with this peptide in combination with pertussis toxin induced high levels of peptide-specific CD4+ T cells in spleen and popliteal lymph nodes. Clinical symptoms of autoimmune neuritis started with a flaccid tail at day 10 postimmunization (p.i.), progressed to moderate paraparesis at day 15 p.i., declining thereafter with undetectable symptoms at day 40 p.i. Clinical disease activity paralleled decreased sciatic nerve motor conduction and histopathologic alterations of sciatic nerves. These included inflammatory infiltrates, mainly consisting of inducible nitric oxide synthase (iNOS)+ macrophages and CD4+ T cells. These data fit into the pathogenetic concept of murine autoimmune neuritis as a CD4+ TH1 cell-mediated disease. Our new mouse model provides an attractive tool to identify critical factors that regulate the severity of autoimmune responses in the peripheral nervous system.
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PMID:P0(106-125) is a neuritogenic epitope of the peripheral myelin protein P0 and induces autoimmune neuritis in C57BL/6 mice. 1571 86


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