Verbout NG

General

Full name : Verbout Norah G

First name : Norah G

Mail : School of Public Health, Harvard University, 665 Huntington Avenue, Boston, MA 02115

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Country : USA

Email : verboutn@ohsu.edu

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References (5)

Title : Muscarinic receptor agonists and antagonists: effects on inflammation and immunity - Verbout_2012_Handb.Exp.Pharmacol_208_403
Author(s) : Verbout NG , Jacoby DB
Ref : Handbook of Experimental Pharmacology , :403 , 2012
Abstract : In this chapter, we will review what is known about muscarinic regulation of immune cells and the contribution of immune cell muscarinic receptors to inflammatory disease and immunity. In particular, immune cell expression of cholinergic machinery, muscarinic receptor subtypes and functional consequences of agonist stimulation will be reviewed. Lastly, this chapter will discuss the potential therapeutic effects of selective antagonists on immune cell function and inflammatory disease in recent animal studies and human clinical trials.
ESTHER : Verbout_2012_Handb.Exp.Pharmacol_208_403
PubMedSearch : Verbout_2012_Handb.Exp.Pharmacol_208_403
PubMedID: 22222708

Title : Role of Rho kinase isoforms in murine allergic airway responses - Zhu_2011_Eur.Respir.J_38_841
Author(s) : Zhu M , Liu PY , Kasahara DI , Williams AS , Verbout NG , Halayko AJ , Fedulov A , Shoji T , Williams ES , Noma K , Shore SA , Liao JK
Ref : Eur Respir J , 38 :841 , 2011
Abstract : Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses. Wildtype (WT) mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1(+/-) and ROCK2(+/-), respectively) were sensitised and challenged with ovalbumin. ROCK expression and activation were assessed by western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment. Compared with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1(+/-) and ROCK2(+/-) mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1(+/-) and ROCK2(+/-) lungs. Airway responsiveness was comparable in WT, ROCK1(+/-), and ROCK2(+/-) mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1(+/-) or ROCK2(+/-) mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1(+/-) and ROCK2(+/-) versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses.
ESTHER : Zhu_2011_Eur.Respir.J_38_841
PubMedSearch : Zhu_2011_Eur.Respir.J_38_841
PubMedID: 21565918

Title : Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects - Moreno-Vinasco_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L340
Author(s) : Moreno-Vinasco L , Verbout NG , Fryer AD , Jacoby DB
Ref : American Journal of Physiology Lung Cell Mol Physiol , 297 :L340 , 2009
Abstract : Inhibitory M(2) muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M(2) receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M(2) receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M(2) receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves, but not to intravenous acetylcholine, indicating that hyperreactivity was due to increased release of acetylcholine from parasympathetic nerves. The muscarinic agonist pilocarpine, which inhibits vagally mediated bronchoconstriction in control animals, no longer inhibited vagally induced bronchoconstriction, demonstrating M(2) receptor dysfunction. Treatment with all-trans retinoic acid (1 mg/kg) prevented virus-induced hyperreactivity and M(2) receptor dysfunction. However, retinoic acid also significantly reduced viral titers in the lungs and attenuated virus-induced lung inflammation. In vitro, retinoic acid decreased M(2) receptor mRNA expression in both human neuroblastoma cells and primary cultures of airway parasympathetic neurons. Thus, the protective effects of retinoic acid on airway function during viral infection appear to be due to anti-inflammatory and antiviral mechanisms, rather than to direct effects on M(2) receptor gene expression.
ESTHER : Moreno-Vinasco_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L340
PubMedSearch : Moreno-Vinasco_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L340
PubMedID: 19465517

Title : Atropine-enhanced, antigen challenge-induced airway hyperreactivity in guinea pigs is mediated by eosinophils and nerve growth factor - Verbout_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L228
Author(s) : Verbout NG , Jacoby DB , Gleich GJ , Fryer AD
Ref : American Journal of Physiology Lung Cell Mol Physiol , 297 :L228 , 2009
Abstract : Although anticholinergic therapy inhibits bronchoconstriction in asthmatic patients and antigen-challenged animals, administration of atropine 1 h before antigen challenge significantly potentiates airway hyperreactivity and eosinophil activation measured 24 h later. This potentiation in airway hyperreactivity is related to increased eosinophil activation and is mediated at the level of the airway nerves. Since eosinophils produce nerve growth factor (NGF), which is known to play a role in antigen-induced airway hyperreactivity, we tested whether NGF mediates atropine-enhanced, antigen challenge-induced hyperreactivity. Antibody to NGF (Ab NGF) was administered to sensitized guinea pigs with and without atropine pretreatment (1 mg/kg iv) 1 h before challenge. At 24 h after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Electrical stimulation of both vagus nerves caused bronchoconstriction that was increased in challenged animals. Atropine pretreatment potentiated antigen challenge-induced hyperreactivity. Ab NGF did not affect eosinophils or inflammatory cells in any group, nor did it prevent hyperreactivity in challenged animals that were not pretreated with atropine. However, Ab NGF did prevent atropine-enhanced, antigen challenge-induced hyperreactivity and eosinophil activation (assessed by immunohistochemistry). This effect was specific to NGF, since animals given control IgG remained hyperreactive. These data suggest that anticholinergic therapy amplifies eosinophil interactions with airway nerves via NGF. Therefore, therapeutic strategies that target both eosinophil activation and NGF-mediated inflammatory processes in allergic asthma are likely to be beneficial.
ESTHER : Verbout_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L228
PubMedSearch : Verbout_2009_Am.J.Physiol.Lung.Cell.Mol.Physiol_297_L228
PubMedID: 19447892

Title : Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism - Verbout_2007_Am.J.Physiol.Lung.Cell.Mol.Physiol_292_L1126
Author(s) : Verbout NG , Lorton JK , Jacoby DB , Fryer AD
Ref : American Journal of Physiology Lung Cell Mol Physiol , 292 :L1126 , 2007
Abstract : Airway hyperreactivity in antigen-challenged animals is mediated by eosinophil major basic protein (MBP) that blocks inhibitory M(2) muscarinic receptors on parasympathetic nerves, increasing acetylcholine release onto M(3) muscarinic receptors on airway smooth muscle. Acutely, anticholinergics block hyperreactivity in antigen-challenged animals and reverse asthma exacerbations in the human, but are less effective in chronic asthma. We tested whether atropine, given before antigen challenge, affected hyperreactivity, M(2) receptor function, eosinophil accumulation, and activation. Sensitized guinea pigs received atropine (1 mg/kg ip) 1 h before challenge and 6 h later. Twenty-four hours after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Airway reactivity to electrical stimulation of the vagi and to intravenous acetylcholine was not altered by atropine pretreatment in nonsensitized animals, indicating that atropine was no longer blocking postjunctional muscarinic receptors. Antigen challenge induced airway hyperreactivity to vagal stimulation that was significantly potentiated by atropine pretreatment. Bronchoconstriction induced by acetylcholine was not changed by antigen challenge or by atropine pretreatment. M(2) receptor function was lost in challenged animals but protected by atropine pretreatment. Eosinophils in bronchoalveolar lavage and within airway tissues were significantly increased by challenge but significantly reduced by atropine pretreatment. However, extracellular MBP in challenged airways was significantly increased by atropine pretreatment, which may account for reduced eosinophils. Depleting eosinophils with antibody to IL-5 before challenge prevented hyperreactivity and significantly reduced MBP in airways of atropine-pretreated animals. Thus atropine pretreatment potentiated airway hyperreactivity by increasing eosinophil activation and degranulation. These data suggest that anticholinergics enhance eosinophil interactions with airway nerves.
ESTHER : Verbout_2007_Am.J.Physiol.Lung.Cell.Mol.Physiol_292_L1126
PubMedSearch : Verbout_2007_Am.J.Physiol.Lung.Cell.Mol.Physiol_292_L1126
PubMedID: 17220376