Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

Tauber, Svantje; Hauschild, Swantje; Paulsen, Katrin; Gutewort, Annett; Raig, Christiane; Hürlimann, Eva; Biskup, Josefine; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Pantaleo, Antonella; Cogoli, Augusto; Pippia, P; Layer, Liliana E.; Thiel, Cora S.; Ullrich, Oliver

doi:10.1159/000373930

Cited by 54 publications

(40 citation statements)

References 46 publications

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“…Downregulation of Nfkb1 has also been reported in the spleen of C57BL/6 mice flown on the Space Shuttle for 13 days [35]. A schematic summary of the influence of microgravity on T lymphocyte function including the inhibition of NF-κB nuclear translocation has been recently reviewed [58]. Nuclear translocation of NF-κB under microgravity does not occur in all cell types.…”

Section: Effects Of Microgravity On Nf-κb In the Immune Systemmentioning

confidence: 99%

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Zhang

Moreno‐Villanueva

Krieger

et al. 2017

IJMS

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In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

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Section: Effects Of Microgravity On Nf-κb In the Immune Systemmentioning

confidence: 99%

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Zhang

Moreno‐Villanueva

Krieger

et al. 2017

IJMS

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“…8 Together, data from the International Space Station, Skylab, and space shuttle suggest that dysregulated immune cell-mediated cytokine secretion is a major mechanism leading to spaceflightassociated immune dysfunction. 5,[9][10][11][12] For example, after space travel, shifts occur in circulating cytokines, including increased levels of T lymphocytes producing IL-4, IL-8, IL-17, and IFN-γ 8,13,14 and decreased production of IL-1, IL-6, IL-12, and TNF-α in monocytes/ macrophages. [15][16][17][18] However, the causes of these immune cell dysfunctions and the associated changes in innate (macrophages and NK cells) and adaptive (T-cell) functions have not been extensively and systematically examined.…”

Section: Introductionmentioning

confidence: 99%

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

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Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

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“…In unseren Studien untersuchten wir Signaltransduktionskaskaden [3,[6][7][8], Adhäsionsmoleküle [9][10][11], Stoffwechsel [11], funktionelle Parameter [12,13], Genexpressionsreaktionen [6,[14][15][16][17][18][19]…”

Section: Erkenntnisse Aus Unseren Studienunclassified

Schnelle zelluläre Reaktion und Anpassung an Schwerelosigkeit

Ullrich

Thiel

2019

Flug u Reisemed

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ZUSAMMENFASSUNGZelluläre Prozesse werden durch Änderungen der Gravitationskraft in vielfältiger Weise beeinflusst. In unseren Studien konnten wir in verschiedenen zellulären Systemen und in verschiedenen Forschungsplattformen (2D Klinostat, Parabelflüge, suborbitale Forschungsraketen, Internationale Raumstation) nachweisen, dass Reaktionen und Anpassungsprozesse bereits innerhalb von Sekunden bis Minuten nach Beginn der veränderten Schwerkraft auftreten. Diese schnellen Prozesse fanden sich in der Genexpression, der Zellzykluskontrolle, der Signaltransduktion, der Zytoskelettorganisation und des oxidativen Burst. Es stellt sich die Frage nach der Ursache der Transduktion einer unspezifischen Kraft in eine hochspezifische zelluläre Antwort, die in der Spezifität der zellulären Eigenschaften begründet liegen kann. Es ist denkbar, dass die Gravitationskraft der Erde die Chromatinarchitektur und deren Zugänglichkeit stabilisiert und eine homöostatische Bedingung für die Genexpression darstellt. Die Untersuchung mechanobiologischer Mechanismen der Genexpression in Schwerelosigkeit kann die Aufdeckung fundamentaler Prinzipien ermöglichen, wie mechanische Kräfte die Zellfunktion regulieren.

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Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

Cited by 54 publications

References 46 publications

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Schnelle zelluläre Reaktion und Anpassung an Schwerelosigkeit

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