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Mediators of Inflammation
Volume 2015 (2015), Article ID 121378, 16 pages
http://dx.doi.org/10.1155/2015/121378
Research Article

Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription Factor T-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis

1Department of Immunology, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic
2IT4Innovations National Supercomputing Center and Faculty of Electrical Engineering and Computer Science, Department of Computer Science, VŠB-Technical University of Ostrava, 70800 Ostrava, Czech Republic
3Department of Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital, 77900 Olomouc, Czech Republic

Received 21 August 2015; Revised 9 October 2015; Accepted 25 October 2015

Academic Editor: Kazuhiro Ito

Copyright © 2015 Tereza Dyskova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing () comparing to regressing () disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as “fine-tuners” of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.