Juan Morán1, Gustavo Ramírez-Martínez2, Luis Jiménez-Alvarez1, Alfredo Cruz1, Santiago Pérez-Patrigeon3, Alfredo Hidalgo4, Lorena Orozco4, Angélica Martínez4, Luis Padilla-Noriega5, Federico Avila-Moreno6, Carlos Cabello1, Julio Granados7, Blanca Ortíz-Quintero1, Alejandra Ramírez-Venegas1, Guillermo M Ruíz-Palacios3, Albert Zlotnik8, Enrique Merino9, Joaquín Zúñiga10. 1. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico. 2. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico. Electronic address: grmunam@yahoo.com.mx. 3. Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico. 4. Instituto Nacional de Medicina Genómica, Mexico City, Mexico. 5. Department of Microbiology and Parasitology, Facultad de Medicina, Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico. 6. FES-Iztacala, Unidad de Biomedicina, UBIMED, Universidad Nacional Autónoma de México, Mexico City, Mexico. 7. Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 8. Department of Biophysics and Physiology, University of California Irvine, CA, USA. 9. Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca City, Mexico. 10. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico. Electronic address: joazu@yahoo.com.
Abstract
BACKGROUND: Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. METHODS: We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. RESULTS: Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically ill patients. CONCLUSION: The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression.
BACKGROUND: Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. METHODS: We studied the circulating and miRNA profiles in critically ill A/H1N1patients, A/H1N1patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. RESULTS:Critically illpatients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically illpatients. CONCLUSION: The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression.
Authors: Carolina N Correia; Nicolas C Nalpas; Kirsten E McLoughlin; John A Browne; Stephen V Gordon; David E MacHugh; Ronan G Shaughnessy Journal: Front Immunol Date: 2017-02-16 Impact factor: 7.561
Authors: Thi Hiep Nguyen; Xiaoming Liu; Zhen Zhong Su; Alan Chen-Yu Hsu; Paul S Foster; Ming Yang Journal: Front Immunol Date: 2018-07-04 Impact factor: 7.561