Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

Autor: Carlos Disdier, Julia Barbado, Felipe Bobillo, Agueda Herrero, Maria C Gallegos, C Alicia San-Jose, Raúl Ortiz de Lejarazu, Jesus F. Bermejo-Martin, Lorenzo Socias, David Andaluz-Ojeda, Vicente Roig, Victoria Fernández, Monica Sanchez-Garcia, Ignacio Martin-Loeches, Sara Rosich, Lucia Rico, Milagros del Olmo, Raquel Almansa
Rok vydání: 2012
Předmět:
Male
Neutrophils
lcsh:Medicine
Cathepsin D
Expression
Cathepsin G
Microarray
Bioinformatics
Severity of Illness Index
Gene
chemistry.chemical_compound
Pulmonary Disease
Chronic Obstructive
Proteinase 3
lcsh:QH301-705.5
Azurocidin 1
Medicine(all)
Neutrophil
General Medicine
Proteases
Middle Aged
Critical
Intensive Care Units
Myeloperoxidase
Female
Genetic Markers
Critical Illness
Short Report
Biology
General Biochemistry
Genetics and Molecular Biology
DEFA3
Humans
COPD
RNA
Messenger
KEGG
lcsh:Science (General)
Aged
Peroxidase
Biochemistry
Genetics and Molecular Biology(all)
Gene Expression Profiling
lcsh:R
Gene expression profiling
lcsh:Biology (General)
chemistry
Gene Expression Regulation
Immunology
biology.protein
Transcriptome
lcsh:Q1-390
Antimicrobial Cationic Peptides
Peptide Hydrolases
Zdroj: BMC Research Notes
BMC Research Notes, Vol 5, Iss 1, p 401 (2012)
ISSN: 1756-0500
Popis: Background Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. Findings By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. Conclusion Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.
Databáze: OpenAIRE
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