Cysteinyl Leukotriene-1 Receptor Activation in a Human Bronchial Epithelial Cell Line Leads to Signal Transducer and Activator of Transcription 1-Mediated Eosinophil Adhesion

Profita, Mirella; Sala, Angelo; Bonanno, Anna; Siena, Liboria; Ferraro, Maria; Giorgi, Rossana Di; Montalbano, Angela Marina; Albano, Giusy Daniela; Gagliardo, Rosalia; Gjomarkaj, Mark

doi:10.1124/jpet.107.131649

Cited by 27 publications

(22 citation statements)

References 42 publications

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“…Montelukast inhibits eosinophil adhesion via several CysLT 1 receptor-dependent mechanisms (17,18). To investigate whether pulmonary inflammation caused by the conditional deletion of Foxa2 in the airway epithelium was associated with activation of the CysLT pathway, Foxa2 D/D mice were treated with montelukast daily from PN5-PN15.…”

Section: Pulmonary Eosinophilic Inflammation Induced By Foxa2 Deletiomentioning

confidence: 99%

Foxa2 Regulates Leukotrienes to Inhibit Th2-mediated Pulmonary Inflammation

Tang¹,

Liu²,

Tian

et al. 2013

Am J Respir Cell Mol Biol

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Foxa2 is a member of the Forkhead family of nuclear transcription factors that is highly expressed in respiratory epithelial cells of the developing and mature lung. Foxa2 is required for normal airway epithelial differentiation, and its deletion causes goblet-cell metaplasia and Th2-mediated pulmonary inflammation during postnatal development. Foxa2 expression is inhibited during aeroallergen sensitization and after stimulation with Th2 cytokines, when its loss is associated with goblet-cell metaplasia. Mechanisms by which Foxa2 controls airway epithelial differentiation and Th2 immunity are incompletely known. During the first 2 weeks after birth, the loss of Foxa2 increases the production of leukotrienes (LTs) and Th2 cytokines in the lungs of Foxa2 gene-targeted mice. Foxa2 expression inhibited 15-lipoxygenase (Alox15) and increased Alox5 transcription, each encoding key lipoxygenases associated with asthma. The inhibition of the cysteinyl LT (CysLT) signaling pathway by montelukast inhibited IL-4, IL-5, eotaxin-2, and regulated upon activation normal T cell expressed and presumably secreted expression in the developing lungs of Foxa2 gene-targeted mice. Montelukast inhibited the expression of genes regulating mucus metaplasia, including Spdef, Muc5ac, Foxa3, and Arg2. Foxa2 plays a cell-autonomous role in the respiratory epithelium, and is required for the suppression of Th2 immunity and mucus metaplasia in the developing lung in a process determined in part by its regulation of the CysLT pathway.

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Section: Pulmonary Eosinophilic Inflammation Induced By Foxa2 Deletiomentioning

confidence: 99%

Foxa2 Regulates Leukotrienes to Inhibit Th2-mediated Pulmonary Inflammation

Tang¹,

Liu²,

Tian

et al. 2013

Am J Respir Cell Mol Biol

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“…Moreover, IL17F induces several cytokines, chemokines and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts and eosinophils [13]. Phosphorylation of STAT1 causes enhanced ICAM1 surface expression and eosinophil adhesion [28]. Also, STAT1 plays a role in promoting the infiltration of leukocytes in experimental hepatitis by stimulating hepatocytes, sinusoidal endothelial cells, and Kupffer cells to produce multiple chemokines and adhesive molecules [12].…”

Section: Discussionmentioning

confidence: 99%

Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cybames Rats Are on Chromosomes 9, 5, and 1

et al. 2011

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Abstract:The Matsumoto Eosinophilia Shinshu (MES) rat strain develops hereditary blood eosinophilia due to the mutant Cyba mes gene. In contrast, BN.MES-Cyba mes congenic rats, in which the mutant Cyba mes gene introduced into the background of the BN strain, have a normal blood eosinophil level despite showing robust proliferation of eosinophils in the bone marrow. However, the congenic rats manifest focal necrosis with eosinophilic infiltration in the liver, a phenotype rarely observed in the original MES rat strain. To elucidate the genetic basis for the strain differences, (MES × BN.MES-Cyba mes )F 2 rats were bred, and genetic analyses of phenotypes for eosinophilia were performed. Blood and bone marrow eosinophil levels in the F 2 rats showed broad distributions, suggesting that the traits were under the influence of multiple genes. Genetic association studies revealed that BN-derived marker loci on chromosomes 9 and 5 were responsible for the increase in eosinophil level in the bone marrow, decrease in blood eosinophil level, and the induction of focal necrosis with eosinophilic infiltration in the liver. The BN-derived allele of the marker gene on chromosome 1 was responsible for the decrease of both bone marrow and blood eosinophil levels. These data suggest the existence of genes characterizing/distinguishing the eosinophilic phenotypes of MES and BN.MES-Cyba mes on these chromosomes, and form the basis for positional cloning studies of the genes. These studies will advance the understanding of the mechanisms involved in eosinophil mobilization from the bone marrow and recruitment to the organs.

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“…CysLTs are reportedly known to increase vascular permeability, neutrophil invasion, and inflammatory cytokine production (Sala and Folco, 2001;Maekawa et al, 2002;Profita et al, 2008). Because I/R-induced damage is a neutrophil-dependent response (Zimmerman and Granger, 1990), it is assumed that the protective effect of pranlukast is brought about, at least Fig.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Importance of Cysteinyl Leukotrienes in Development of Gastric Lesions Induced by Ischemia/Reperfusion in Mice

Nakamori

Komatsu

Kotani

et al. 2009

J Pharmacol Exp Ther

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We examined the role of cysteinyl leukotrienes (CysLTs) in the gastric ulcerogenic response to ischemia/reperfusion (I/R) in mice. Experiments were performed in male C57BL/6J mice after 18-h fasting. Under urethane anesthesia, the celiac artery was clamped for 30 min, and then reperfusion was achieved by removing the clamp. The stomach was examined for lesions 60 min thereafter. The severity of I/R-induced gastric damage was reduced by prior administration of pranlukast [CysLT receptorOn the contrary, these lesions were markedly worsened by pretreatment with indomethacin, and this response was abrogated by the coadministration of TMK688 or pranlukast. The gene expression of CysLT 1 R but not 5-LOX was up-regulated in the stomach after I/R, but both expressions were increased under I/R in the presence of indomethacin. I/R slightly increased the mucosal CysLT content of the stomach, yet this increase was markedly enhanced when the animals were pretreated with indomethacin. The increased CysLT biosynthetic response to indomethacin during I/R was attenuated by TMK688. Indomethacin alone caused a slight increase of CysLT 1 R expression and markedly up-regulated 5-LOX expression in the stomach. We concluded that I/R up-regulated the expression of CysLT 1 R in the stomach; CysLTs play a role in the pathogenesis of I/R-induced gastric damage through the activation of CysLT 1 R; and the aggravation by indomethacin of these lesions may be brought about by the increase of CysLT production and the up-regulation of 5-LOX expression, in addition to the decreased prostaglandin production.

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Cysteinyl Leukotriene-1 Receptor Activation in a Human Bronchial Epithelial Cell Line Leads to Signal Transducer and Activator of Transcription 1-Mediated Eosinophil Adhesion

Cited by 27 publications

References 42 publications

Foxa2 Regulates Leukotrienes to Inhibit Th2-mediated Pulmonary Inflammation

Foxa2 Regulates Leukotrienes to Inhibit Th2-mediated Pulmonary Inflammation

Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cybames Rats Are on Chromosomes 9, 5, and 1

Pathogenic Importance of Cysteinyl Leukotrienes in Development of Gastric Lesions Induced by Ischemia/Reperfusion in Mice

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