Dataset Information

IL-10 Dysregulation in Acute Mountain Sickness Revealed by Transcriptome Analysis.

ABSTRACT: Acute mountain sickness (AMS), which may progress to life-threatening high-altitude cerebral edema, is a major threat to millions of people who live in or travel to high altitude. Although studies have revealed the risk factors and pathophysiology theories of AMS, the molecular mechanisms of it do not comprehensively illustrate. Here, we used a system-level methodology, RNA sequencing, to explore the molecular mechanisms of AMS at genome-wide level in 10 individuals. After exposure to high altitude, a total of 1,164 and 1,322 differentially expressed transcripts were identified in AMS and non-AMS groups, respectively. Among them, only 328 common transcripts presented between the two groups. Immune and inflammatory responses were overrepresented in participants with AMS, but not in non-AMS individuals. Anti-inflammatory cytokine IL10 and inflammation cytokines IF17F and CCL8 exhibited significantly different genetic connectivity in AMS compared to that of non-AMS individuals based on network analysis. IL10 was downregulated and both IF17F and CCL8 were upregulated in AMS individuals. Moreover, the serum concentration of IL10 significantly decreased in AMS patients after exposure to high altitude (p?=?0.001) in another population (n?=?22). There was a large negative correlation between the changes in IL10 concentration, r(22)?=?-0.52, p?=?0.013, and Lake Louise Score. Taken together, our analysis provides unprecedented characterization of AMS transcriptome and identifies that genes involved in immune and inflammatory responses were disturbed in AMS individuals by high-altitude exposure. The reduction of IL10 after exposure to high altitude was associated with AMS.

SUBMITTER: Liu B

PROVIDER: S-EPMC5447681 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-10 Dysregulation in Acute Mountain Sickness Revealed by Transcriptome Analysis.

Liu Bao B Chen Jian J Zhang Long L Gao Yixing Y Cui Jianhua J Zhang Erlong E Xu Gang G Liang Yan Y Liang Yu Y Wang Jian J Gao Yuqi Y

Frontiers in immunology 20170530

Acute mountain sickness (AMS), which may progress to life-threatening high-altitude cerebral edema, is a major threat to millions of people who live in or travel to high altitude. Although studies have revealed the risk factors and pathophysiology theories of AMS, the molecular mechanisms of it do not comprehensively illustrate. Here, we used a system-level methodology, RNA sequencing, to explore the molecular mechanisms of AMS at genome-wide level in 10 individuals. After exposure to high altit ...[more]

PMID: 28611780

Similar Datasets

Project description:Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

Dataset Information

IL-10 Dysregulation in Acute Mountain Sickness Revealed by Transcriptome Analysis.

Publications

IL-10 Dysregulation in Acute Mountain Sickness Revealed by Transcriptome Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets