Page 156 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

through the small GTPase Rac. Rac is a pleiotropic regulator of many cellular processes, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases and phospholipase A2[67]. Gene expression profiling in osteoblasts identified especially cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA as being negatively targeted by microgravity[34], which are genes whose expression is downstream of the Rac effector pathways involving activation of the p38 MAPK and Jun-N-terminal kinases. Production of phospholipase A2-dependent pro-inflammatory lipid mediators is negatively affected by microgravity (Gravit Physiol. 2004 Jul;11(2): P41-2. Effect of simulated microgravity on PGE2-induced edema and hyperalgesia in rat paws: pharmacological data and biochemical correlates. Peana AT, Bennardini F, Buttu L, Pippia P, Meloni MA, Stuffler RG, Maccarrone M.). Also, the cytoskeletal effects of microgravity on growth factor-induced cytoskeletal remodeling seem consistent with an impact on Rac activation[68]. (Describe effects of expression of Rac. Inhibitory action of microgravity would fit well with differential effects of microgravity on alternative immunological compartments, whereas moderate Rac inhibition leads to diminished action of the adaptive immune system, such inhibition enhances effector function in phagocytes). Hence microgravity mirrors essential aspects of the known consequences of Rac inhibition on the immune system and it should prove interesting to directly assess the influence of space flight on GTP-loading of this GTPase or the phosphorylation state of its direct effectors, the p21-activated kinases (or PAKs).
Effect of space flight-associated microgravity on stress-activated protein kinases in innate immunity.
Spaceflight actively moderates human immunity but is in general well tolerated. Elucidation of the mechanisms by which zero gravity interacts with human immunity may provide clues for developing rational avenues to deal with exaggerated immune responses, e.g., as in autoimmune disease[69]. The human immune system, like all cell biological systems in our body, has developed in the continuous presence of the earth’s gravitational field. Thus it is conceivable that acute absence of this external force, as occurs during space flight, would influence functionality in this system. Indeed since the early days of space exploration, it has been evident that extra-atmospheric primates and humans experience reduced immune function[13, 21, 70].
Chapter 7
Chapter 7
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