Page 157 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Activation of p38 map kinase is not affected by space flight associated microgravity.
One of the most notable biochemical changes following LPS challenge is the phosphorylation and thereby activation of p38 MAP kinase[71, 72]. Inhibition of p38 MAP kinase protects against endotoxemia in LPS challenged healthy volunteers[72], although clinical implementation of pharmacological p38 MAP kinase inhibition has not proven viable because of side effects and extreme vulnerability towards bacterial infection. Various genes, like PRKCA22, whose expression is known to be exquisitely sensitive to microgravity are identified to be regulated by p38 MAP kinase[73]. Hence, it is conceivable that activation of p38 MAPK is impaired during microgravity. As expected, the onboard 1xg control displayed p38 MAP kinase activation. In contrast, activation of p38 MAP kinase was not impaired in microgravity-exposed monocytes, if anything p38 MAP kinase activation appears to be increased. Thereby suggesting that space flight-associated microgravity does not interfere with LPS-induced pro- inflammatory signal transduction per se and its effects, if present, are restricted to specific signaling pathways.
LPS does not activate Jun-n-terminal kinase during space flight associated microgravity.
In general inflammatory stimuli coactivate p38 MAP kinase and Jun-N-terminal kinase, as activation of both kinases displays similar kinetics[74]. Nevertheless, they are activated by different upstream kinases (MKK3/6 and MKK4/7 for p38 MAP kinase and Jun-N-terminal kinase, respectively[75]. Thus, at least theoretically, the possibility exists that space flight-associated microgravity targets Jun-N-terminal kinase without a concomitant effect on p38 MAP kinase. Surprisingly, during microgravity, the capacity of LPS to stimulate Jun-N-terminal kinase activation is lost, whereas monocytes stimulated with LPS during the onboard control condition were utterly Jun-N-terminal kinase activation proficient. Thus, microgravity evokes a dichotomy in immunological signaling, allowing p38 MAP kinase activation to proceed, but incompatible with LPS dependent Jun-N-terminal kinase activation. Although it does not involve immunologically relevant cells, the observation that the induction of c-Jun in A431 cells by epidermal growth factor is absent in microgravity[32], fits well with our findings. Especially since it has been well established that Jun-N-terminal kinase is involved in the induction of c-Jun and p38 MAPK is not.
Health from above?
Health from above?
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