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Neurogastroenterol Motil. 2017 Jun;29(6). doi: 10.1111/nmo.13027. Epub 2017 Feb 12.

Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study.

Gupta A1,2,3, Cole S2,4, Labus JS1,2,3, Joshi S1,2,3,5, Nguyen TJ1, Kilpatrick LA1,2,3, Tillisch K1,2,3,6, Naliboff BD1,2,3, Chang L1,2,3, Mayer EA1,2,3,7.

Author information

1
Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.
2
David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
3
Vatche and Tamar Manoukin Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
4
Department of Hematology-Oncology, UCLA, Los Angeles, CA, USA.
5
Center for Systems Biomedicine, UCLA, Los Angeles, CA, USA.
6
Integrative Medicine, GLA, VHA, Los Angeles, CA, USA.
7
Ahmanson-Lovelace Brain Mapping Center, UCLA, Los Angeles, CA, USA.

Abstract

BACKGROUND:

Distinct gene expression profiles in peripheral blood mononuclear cells (PBMCs) consistent with increased sympathetic nervous system activity have been described in different populations under chronic stress. Neuroinflammatory brain changes, possibly related to the migration of primed monocytes to the brain, have been implicated in the pathophysiology of chronic pain. Irritable bowel syndrome (IBS) is a stress-sensitive gastrointestinal disorder associated with altered brain-gut interactions and increased sympathetic/vagal tone and anxiety. Reports about immune alterations in IBS are conflicting. This pilot study aimed to test how PBMC gene expression inflammatory profiles are correlated with altered brain signatures in the salience system.

METHODS:

Sixteen IBS and 16 healthy controls (HCs) completed resting state MRI scans. Gene expression profiles in PBMCs were assessed using human transcriptome array-2. Bioinformatic analyses determined differential expression of PBMCs between IBS and HCs. Partial least squares, a multivariate analysis technique, was used to identify disease correlations between PBMC gene expression profiles and functional activity in the brain's salience network.

KEY RESULTS:

Regions of the salience network, including the mid cingulate cortex, and mid and superior temporal gyrus were positively correlated with several pro-inflammatory genes (interleukin 6, APOL2) in IBS, but negatively correlated with several anti-inflammatory genes (KRT8, APOA4) in HCs.

CONCLUSIONS & INFERENCES:

Based on rodent studies, one may speculate that chronically activated stress signaling pathways in IBS maintain a pro-inflammatory state in the periphery. Alternatively, primed monocytes may migrate to the brain during stress, inducing regional neuroinflammatory changes in salience regions involved in the modulation of visceral sensitivity.

KEYWORDS:

anti-inflammatory genes; chronic visceral pain syndrome; immune system; peripheral blood mononuclear cells; pro-inflammatory genes; resting state brain activity; salience network

PMID:
28191693
PMCID:
PMC5503466
DOI:
10.1111/nmo.13027
[Indexed for MEDLINE]
Free PMC Article

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