Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial

Kammerer, Tobias; Faihs, Valentina; Hulde, Nikolai; Stangl, Manfred; Brettner, Florian; Rehm, Markus; Horstmann, Mareike; Kroepfl, Julia; Spengler, Christina; Kreth, Simone und Schaefer, Simon (2020): Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial. In: International Journal of Molecular Sciences, Bd. 21, Nr. 3, 1034

Abstract

Induction of hypoxia-inducible-factor-1 alpha (HIF-1 alpha) pathway and HIF-target genes allow adaptation to hypoxia and are associated with reduced incidence of acute mountain sickness (AMS). Little is known about HIF-pathways in conjunction with inflammation or exercise stimuli under acute hypobaric hypoxia in non-acclimatized individuals. We therefore tested the hypotheses that (1) both hypoxic and inflammatory stimuli induce hypoxic-inflammatory signaling pathways in vitro, (2) similar results are seen in vivo under hypobaric hypoxia, and (3) induction of HIF-dependent genes is associated with AMS in 11 volunteers. In vitro, peripheral blood mononuclear cells (PBMCs) were incubated under hypoxic (10%/5% O-2) or inflammatory (CD3/CD28) conditions. In vivo, Interleukin 1 beta (IL-1 beta), C-X-C Chemokine receptor type 4 (CXCR-4), and C-C Chemokine receptor type 2 (CCR-2) mRNA expression, cytokines and receptors were analyzed under normoxia (520 m above sea level (a.s.l.)), hypobaric hypoxia (3883 m a.s.l.) before/after exercise, and after 24 h under hypobaric hypoxia. In vitro, isolated hypoxic (p = 0.004) or inflammatory (p = 0.006) stimuli induced IL-1 beta mRNA expression. CCR-2 mRNA expression increased under hypoxia (p = 0.005);CXCR-4 mRNA expression remained unchanged. In vivo, cytokines, receptors, and IL-1 beta, CCR-2 and CXCR-4 mRNA expression increased under hypobaric hypoxia after 24 h (all p <= 0.05). Of note, proinflammatory IL-1 beta and CXCR-4 mRNA expression changes were associated with symptoms of AMS. Thus, hypoxic-inflammatory pathways are differentially regulated, as combined hypoxic and exercise stimulus was stronger in vivo than isolated hypoxic or inflammatory stimulation in vitro.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch