Pluto Bioinformatics

GSE75665: A strong relatedness between interleukin-10 and acute mountain sickness revealed by transcriptome analysis

Bulk RNA sequencing

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 down-regulated and both IF17F and CCL8 were un-regulated 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 of 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. Among them, the reduction of IL10 after exposure to high altitude may responsible for the pathogenesis of AMS.Conclusion: Inflammatory and immune responses are important pathophysiological processes in AMS. Suppression of the anti-inflammatory response, caused by reduced IL10 production, may be critical in AMS pathogenesis. Our findings reveal a new direction for AMS pathogenesis investigation, which may be useful for developing pharmacological prophylaxis and treatment. SOURCE: bao liu (lb_tmmu@yeah.net) - Key Laboratory of High Altitude Medicine, Ministry of Education 3rd Military Medical University