title: Dichotomal effect of space flight-associated microgravity on stress-activated protein kinases in innate immunity.
abstract: Space flight strongly 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. Using two sounding rockets and one manned Soyuz launch, the influence of space flight on immunological signal transduction provoked by lipopolysaccharide (LPS) stimulation was investigated in freshly isolated peripheral blood monocytes and was compared to samples obtained from on-board centrifuge-loaded 1 g controls. The effect of microgravity on immunological signal transduction is highly specific, since LPS dependent Jun-N-terminal kinase activation is impaired in the 0 g condition, while the corresponding LPS dependent activation of p38 MAP kinase remains unaffected. Thus our results identify Jun-N-terminal kinase as a relevant target in immunity for microgravity and support using Jun-N-terminal kinase specific inhibitors for combating autoimmune disease.
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Auke P
authors: AP
authors: Verhaar
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Elmer
authors: E
authors: Hoekstra
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Angela S W
authors: AS
authors: Tjon
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Wesley K
authors: WK
authors: Utomo
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: J Jasper
authors: JJ
authors: Deuring
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Elvira R M
authors: ER
authors: Bakker
authors: Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Centre, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands.
authors: Vanesa
authors: V
authors: Muncan
authors: Department of Gastroenterology and Hepatology. Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
authors: Maikel P
authors: MP
authors: Peppelenbosch
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007124:Immunoenzyme Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013026:Space Flight; D013312:Stress, Physiological; D014893:Weightlessness; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases