Immune response in microgravity: genetic basis and countermeasure development implications.
- Paper number
IAC-06-A1.P.1.10
- Author
Dr. Diana Risin, National Aeronautics and Space Administration (NASA)/Johnson Space Center, United States
- Coauthor
Dr. Nancy Ward, Wyle Laboratories, United States
- Coauthor
Dr. Semyon A. Risin, United States
- Coauthor
Dr. Neal R. Pellis, National Aeronautics and Space Administration (NASA)/Johnson Space Center, United States
- Year
2006
- Abstract
Impairment of the immunity in astronauts and cosmonauts even in short-term flights is a recognized risk. Long-term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Studies in true and modeled microgravity (MG) have demonstrated that MG directly affects numerous lymphocyte functions. The purpose of this study was to screen for genes involved in lymphocytes response to modeled microgravity (MMG) that could explain the functional and structural changes observed earlier. The microgravity-induced changes in gene expression were analyzed by microarray DNA chip technology. CD3- and IL2-activated T-cells were cultured in 1g (static) and modeled microgravity (NASA Rotating Wall Vessel bioreactor) conditions for 24 hours. Total RNA was extracted using the RNeasy isolation kit (Qiagen, Valencia, CA). Microarray experiments were performed utilizing Affymetrix Gene Chips (U133A), allowing testing for 18,400 human genes. To decrease the biological variation and aid in detecting microgravity-associated changes, experiments were performed in triplicate using cells obtained from three different donors. Exposure to modeled microgravity resulted in alteration of 89 genes, 10 of which were up-regulated and 79 down-regulated. Altered genes were categorized by their function, structural role and by association with metabolic and regulatory pathways. A large proportion was found to be involved in fundamental cellular processes: signal transduction, DNA repair, apoptosis, and multiple metabolic pathways. There was a group of genes directly related to immune and inflammatory responses (IL-7R, granulysin, proteasome activator subunit 2, peroxiredoxin 4, HLA-DRA, lymphocyte antigen 75, IL-18R and DOCK2 genes). Among these genes only one (IL-7R) was up-regulated, the rest were down-regulated. The up-regulation of the IL-7 receptor gene was confirmed by RT PCR. Three genes with altered expression were identified in the apoptosis related group (Granzyme B, APO-2 ligand and Beta-3-endonexin). All of them were down-regulated. Gene expression changes in MG might appear pivotal in identifying potential molecular targets for countermeasure development. (Supported by NRA OLMSA-02 and NSCORT NAG5-4072 grants).
- Abstract document