Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma

Owen, Helen C., Torrance, Hew D. T., Jones, Timothy F., Pearse, Rupert M., Hinds, Charles J., Brohi, Karim and O'Dwyer, Michael J. (2015) Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma. Journal of Trauma and Acute Care Surgery, 79 (5). pp. 766-772. ISSN 2163-0755 (doi:10.1097/TA.0000000000000850)

[img]
Preview
PDF - Final accepted version (with author's formatting)
Download (310kB) | Preview

Abstract

BACKGROUND

Posttraumatic nosocomial pneumonia is a common complication resulting in significant morbidity. Trauma-induced immunocompromise is associated with an enhanced susceptibility to pneumonia. In this study, we explore the hypothesis that posttranscriptional epigenetic regulation of gene expression may be an important factor in determining this immune phenotype. We describe the pattern of production of microRNAss (miRs) and their association with nosocomial pneumonia following severe trauma.

METHODS

A convenience sample of 30 ventilated polytrauma patients (UKCRN ID: 5637) and 16 healthy controls were recruited. Messenger RNA and protein levels of key cytokines were quantified within 2 hours of the injury and at 24 hours. Three miRs per cytokine were then selected based on miRBase target prediction scores and quantified using polymerase chain reaction. Nosocomial pneumonia was defined using the Centers for Disease Control and Prevention definitions.

RESULTS

Median Injury Severity Score (ISS) was 29, and 47% of the patients developed nosocomial pneumonia. miR-125a and miR-202 decreased by 34% and 77%, respectively, immediately following injury, whereas their target, IL-10, increased messenger RNA levels 3-fold and protein levels 180 fold. Tumor necrosis factor α (TNF-α) and IL-12 gene expression decreased by 68% and 43%, respectively, following injury, and this was mirrored by a 10-fold increase in miR-181, an miR predicted to target TNF-α transcripts. Lower levels of miR-125a and miR-374b were associated with the later acquisition of hospital-acquired pneumonia.

CONCLUSION

Alteration in the expression of miRs with highly predicted complementarity to IL-10 and TNF-α may be an important mechanism regulating the posttraumatic immunosuppressive phenotype in intensive care unit patients.

LEVEL OF EVIDENCE

Retrospective observational study, level III.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 19093
Notes on copyright: Attached full text:- This is a non-final version of an article published in final form in Owen, H., Torrance, H., Jones, T., Pearse, R., Hinds, C., Brohi, K., & O'Dwyer, M. (2015). Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma. Journal of Trauma and Acute Care Surgery, 79(5), 766-772. doi:10.1097/TA.0000000000000850.
Useful Links:
Depositing User: Helen Roberts
Date Deposited: 08 Apr 2016 10:32
Last Modified: 31 May 2019 02:45
URI: https://eprints.mdx.ac.uk/id/eprint/19093

Actions (login required)

Edit Item Edit Item

Full text downloads (NB count will be zero if no full text documents are attached to the record)

Downloads per month over the past year