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Immune Response in Microgravity: Genetic Basis and Countermeasure Development ImplicationsImpairment of the immunity in astronauts and cosmonauts even in shortterm flights is a recognized risk. Longterm 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. CD3and IL2activated Tcells 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 upregulated 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 (IL7R, granulysin, proteasome activator subunit 2, peroxiredoxin 4, HLADRA, lymphocyte antigen 75, IL18R and DOCK2 genes). Among these genes only one (IL7R) was upregulated, the rest were downregulated. The upregulation of the IL7 receptor gene was confirmed by RT PCR. Three genes with altered expression were identified in the apoptosis related group (Granzyme B, APO2 ligand and Beta3endonexin). All of them were downregulated. Gene expression changes in MG might appear pivotal in identifying potential molecular targets for countermeasure development. (Supported by NRA OLMSA02 and NSCORT NAG54072 grants).
Document ID
20080026054
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Risin, Diana
(NASA Johnson Space Center Houston, TX, United States)
Ward, Nancy E.
(Wyle Life Sciences, Inc. Houston, TX, United States)
Risin, Semyon A.
(Texas Univ. Houston, TX, United States)
Pellis, Neal R.
(NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 24, 2013
Publication Date
October 2, 2006
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 57th International Astronautical Congress
Location: Valencia
Country: Spain
Start Date: October 2, 2006
End Date: October 6, 2006
Funding Number(s)
CONTRACT_GRANT: NRA OLMSA-02
CONTRACT_GRANT: NAG5-4072
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.

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