title: Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology.
abstract: Sepsis is a major cause of death worldwide. It triggers systemic inflammation, the role of which remains unclear. In the current study, we investigated the induction of microRNA (miRNA) during sepsis and their role in the regulation of inflammation. Patients, on days 1 and 5 following sepsis diagnosis, had reduced T cells but elevated monocytes. Plasma levels of IL-6, IL-8, IL-10 and MCP-1 dramatically increased in sepsis patients on day 1. T cells from sepsis patients differentiated primarily into Th2 cells, whereas regulatory T cells decreased. Analysis of 1163 miRNAs from PBMCs revealed that miR-182, miR-143, miR-145, miR-146a, miR-150, and miR-155 were dysregulated in sepsis patients. miR-146a downregulation correlated with increased IL-6 expression and monocyte proliferation. Bioinformatics analysis uncovered the immunological associations of dysregulated miRNAs with clinical disease. The current study demonstrates that miRNA dysregulation correlates with clinical manifestations and inflammation, and therefore remains a potential therapeutic target against sepsis.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA; Institute for Tumor Immunology, Ludong University School of Life Sciences, Yantai, Shandong 264025, PR China.
authors.forename: Juhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Hina
authors.initials: H
authors.lastname: Chaudhry
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Mir Mustafa
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Perkins
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Owens
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Morales
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: McGuire
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Zumbrun
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA. Electronic address: Mitzi.Nagarkatti@uscmed.sc.edu.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
mesh_terms: D000368:Aged; D002454:Cell Differentiation; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D019295:Computational Biology; D016207:Cytokines / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018805:Sepsis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; C542542:MIRN146 microRNA, human; D035683:MicroRNAs
keywords: Cytokine; Monocyte; Sepsis; miR-146a; miRNA