<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bezzerri, Valentino</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">Rimessi, Alessandro</style></author><author><style face="normal" font="default" size="100%">Lanzara, Carmen</style></author><author><style face="normal" font="default" size="100%">Crovella, Sergio</style></author><author><style face="normal" font="default" size="100%">Nicolis, Elena</style></author><author><style face="normal" font="default" size="100%">Tamanini, Anna</style></author><author><style face="normal" font="default" size="100%">Athanasakis, Emmanouil</style></author><author><style face="normal" font="default" size="100%">Tebon, Maela</style></author><author><style face="normal" font="default" size="100%">Bisoffi, Giulia</style></author><author><style face="normal" font="default" size="100%">Drumm, Mitchell L</style></author><author><style face="normal" font="default" size="100%">Knowles, Michael R</style></author><author><style face="normal" font="default" size="100%">Pinton, Paolo</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Berton, Giorgio</style></author><author><style face="normal" font="default" size="100%">Cabrini, Giulio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Phospholipase C-β3 is a key modulator of IL-8 expression in cystic fibrosis bronchial epithelial cells.</style></title><secondary-title><style face="normal" font="default" size="100%">J Immunol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Immunol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adenosine Triphosphate</style></keyword><keyword><style  face="normal" font="default" size="100%">Calcium</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Transformed</style></keyword><keyword><style  face="normal" font="default" size="100%">Cystic Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Enzyme Activation</style></keyword><keyword><style  face="normal" font="default" size="100%">Epithelial Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Green Fluorescent Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Host-Pathogen Interactions</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Interleukin-8</style></keyword><keyword><style  face="normal" font="default" size="100%">Isoenzymes</style></keyword><keyword><style  face="normal" font="default" size="100%">Lung Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Microscopy, Fluorescence</style></keyword><keyword><style  face="normal" font="default" size="100%">Phospholipase C beta</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Kinase C</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Kinase C beta</style></keyword><keyword><style  face="normal" font="default" size="100%">Pseudomonas aeruginosa</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA Interference</style></keyword><keyword><style  face="normal" font="default" size="100%">Toll-Like Receptors</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factor RelA</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Apr 15</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">186</style></volume><pages><style face="normal" font="default" size="100%">4946-58</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Respiratory insufficiency is the major cause of morbidity and mortality in patients affected by cystic fibrosis (CF). An excessive neutrophilic inflammation, mainly orchestrated by the release of IL-8 from bronchial epithelial cells and amplified by chronic bacterial infection with Pseudomonas aeruginosa, leads to progressive tissue destruction. The anti-inflammatory drugs presently used in CF patients have several limitations, indicating the need for identifying novel molecular targets. To address this issue, we preliminarily studied the association of 721 single nucleotide polymorphisms from 135 genes potentially involved in signal transduction implicated in neutrophil recruitment in a cohort of F508del homozygous CF patients with either severe or mild progression of lung disease. The top ranking association was found for a nonsynonymous polymorphism of the phospholipase C-β3 (PLCB3) gene. Studies in bronchial epithelial cells exposed to P. aeruginosa revealed that PLCB3 is implicated in extracellular nucleotide-dependent intracellular calcium signaling, leading to activation of the protein kinase Cα and Cβ and of the nuclear transcription factor NF-κB p65. The proinflammatory pathway regulated by PLCB3 acts by potentiating the Toll-like Receptors' signaling cascade and represents an interesting molecular target to attenuate the excessive recruitment of neutrophils without completely abolishing the inflammatory response.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21411730?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Crovella, Sergio</style></author><author><style face="normal" font="default" size="100%">Segat, Ludovica</style></author><author><style face="normal" font="default" size="100%">Amato, Annalisa</style></author><author><style face="normal" font="default" size="100%">Athanasakis, Emmanouil</style></author><author><style face="normal" font="default" size="100%">Bezzerri, Valentino</style></author><author><style face="normal" font="default" size="100%">Braggion, Cesare</style></author><author><style face="normal" font="default" size="100%">Casciaro, Rosaria</style></author><author><style face="normal" font="default" size="100%">Castaldo, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Colombo, Carla</style></author><author><style face="normal" font="default" size="100%">Covone, Angela Elvira</style></author><author><style face="normal" font="default" size="100%">De Rose, Virginia</style></author><author><style face="normal" font="default" size="100%">Gagliardini, Rolando</style></author><author><style face="normal" font="default" size="100%">Lanzara, Carmen</style></author><author><style face="normal" font="default" size="100%">Minicucci, Laura</style></author><author><style face="normal" font="default" size="100%">Morgutti, Marcello</style></author><author><style face="normal" font="default" size="100%">Nicolis, Elena</style></author><author><style face="normal" font="default" size="100%">Pardo, Francesca</style></author><author><style face="normal" font="default" size="100%">Quattrucci, Serena</style></author><author><style face="normal" font="default" size="100%">Raia, Valeria</style></author><author><style face="normal" font="default" size="100%">Ravazzolo, Roberto</style></author><author><style face="normal" font="default" size="100%">Seia, Manuela</style></author><author><style face="normal" font="default" size="100%">Stanzial, Valentino</style></author><author><style face="normal" font="default" size="100%">Termini, Lisa</style></author><author><style face="normal" font="default" size="100%">Zazzeron, Laura</style></author><author><style face="normal" font="default" size="100%">Cabrini, Giulio</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients.</style></title><secondary-title><style face="normal" font="default" size="100%">Clin Chem Lab Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Clin. Chem. Lab. Med.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">5' Untranslated Regions</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">beta-Defensins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cystic Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cystic Fibrosis Transmembrane Conductance Regulator</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Homozygote</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Italy</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">49</style></volume><pages><style face="normal" font="default" size="100%">49-54</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G&gt;A, c.-44C&gt;G and c.-20G&gt;A) in the 5' untranslated region (5' UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42).&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;For the c.-20G&gt;A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G&gt;A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21077791?dopt=Abstract</style></custom1></record></records></xml>