Page 153 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

conditions it is sometimes tricky to detect reflections of pathology in the cytokine profile of peripheral blood in the absence of fulminant disease[58]. Nevertheless, despite 30 years of frantic research and experimentation, there is no evidence that microgravity-related immunosuppression can be linked to changes in the external milieu.
It is important to note however, that changes in intracellular signalling and extracellular milieu can never be regarded separately, as diminished intracellular signalling will result in diminished cytokine production, in turn affecting downstream responses and feedback loops, e.g., Con-A stimulated interleukin 2 secretions by T lymphocytes is negatively affected by simulated microgravity and this will without doubt aid the reduced mitogenic responsiveness to Con-A during microgravity in this cellular compartment[59]. Nevertheless, altered responsiveness to extracellular cues rather than a difference in the extracellular environment explains why immune cells behave differently during autoimmunity, focussing studies towards the influence of microgravity on cell-autonomous mechanisms. Some studies also found that LPS- induced TNF-α expression in mouse macrophages was significantly suppressed under simulated microgravity. NF-κB activation and TNF-α mRNA stability were resistant to microgravity. The repressor of TNF-α promoter, HSF1, which was activated under simulated microgravity, may be one of the critical mechanisms for the reduced TNF-α expression in macrophages under microgravity[60]. The oxidative burst reaction in mammalian cells, necessary for example for the internalization and degradation of bacteria, depends on the presence of gravity[61]. The release of reactive oxygen species (ROS) during the oxidative burst reaction depends on gravity conditions. ROS release is 1.) reduced in microgravity, 2.) enhanced in hypergravity and 3.) responds rapidly and reversible to altered gravity within seconds. We substantiated the effect of altered gravity on oxidative burst reaction in two independent experimental systems, parabolic flights, and 2D clinostat/centrifuge experiments. Furthermore, the results obtained in simulated microgravity (2D clino-rotation experiments) were validated by experiments in real microgravity, in both cases showing a pronounced reduction in ROS. Our analyses indicate that gravity-sensitive steps are located both in the initial activation pathways and in the final oxidative burst reaction itself, which could be explained by the role of cytoskeletal dynamics in the assembly and functionality of the NADPH oxidase complex[61].
Health from above?
Health from above?
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