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Article

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

1
Institute of Anesthesiology, Heart and Diabetes Center NRW, Ruhr-University Bochum, Georgstr. 11, 32545 Bad Oeynhausen, Germany
2
Department of Anaesthesiology, University Hospital, LMU Munich, 81377 Munich, Germany
3
Walter Brendel Centre of Experimental Medicine, LMU Munich, 81377 Munich, Germany
4
Klinik für Allgemein-, Viszeral-, und Transplantationschirurgie, LMU Munich, 81377 Munich, Germany
5
Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, 45147 Essen, Germany
6
Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich, 8057 Zurich, Switzerland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1034; https://doi.org/10.3390/ijms21031034
Received: 12 December 2019 / Revised: 29 January 2020 / Accepted: 1 February 2020 / Published: 4 February 2020
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
Induction of hypoxia-inducible-factor-1α (HIF-1α) 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% O2) or inflammatory (CD3/CD28) conditions. In vivo, Interleukin 1β (IL-1β), 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-1β mRNA expression. CCR-2 mRNA expression increased under hypoxia (p = 0.005); CXCR-4 mRNA expression remained unchanged. In vivo, cytokines, receptors, and IL-1β, CCR-2 and CXCR-4 mRNA expression increased under hypobaric hypoxia after 24 h (all p ≤ 0.05). Of note, proinflammatory IL-1β 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. View Full-Text
Keywords: hypoxic-inflammatory response; hypobaric hypoxia; cytokines hypoxic-inflammatory response; hypobaric hypoxia; cytokines
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MDPI and ACS Style

Kammerer, T.; Faihs, V.; Hulde, N.; Stangl, M.; Brettner, F.; Rehm, M.; Horstmann, M.; Kröpfl, J.; Spengler, C.; Kreth, S.; Schäfer, S. Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial. Int. J. Mol. Sci. 2020, 21, 1034. https://doi.org/10.3390/ijms21031034

AMA Style

Kammerer T, Faihs V, Hulde N, Stangl M, Brettner F, Rehm M, Horstmann M, Kröpfl J, Spengler C, Kreth S, Schäfer S. Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial. International Journal of Molecular Sciences. 2020; 21(3):1034. https://doi.org/10.3390/ijms21031034

Chicago/Turabian Style

Kammerer, Tobias, Valentina Faihs, Nikolai Hulde, Manfred Stangl, Florian Brettner, Markus Rehm, Mareike Horstmann, Julia Kröpfl, Christina Spengler, Simone Kreth, and Simon Schäfer. 2020. "Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial" International Journal of Molecular Sciences 21, no. 3: 1034. https://doi.org/10.3390/ijms21031034

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