Effect of TNF-α on CD3-ζ and MHC-I in postnatal rat hippocampus

Abstract

The ζ subunit of the CD3 T-cell receptor complex and the major histocompatibility complex class 1 (MHC-I) are important not only for the immune response to antigens, they also function as signal molecules in the brain, where they play a role in the postnatal maturation process. The expression of these molecules can be regulated by cytokines. In situations associated with increased cytokine production, such as neonatal hypoxia, the hippocampus is particularly susceptible to permanent damage. This has prompted us to examine the MHC-I and CD3-ζ expression in hippocampus from early postnatal, weanling and adolescent rats and to record the effects of TNF-α and IL-1β, cytokines commonly increased in neonatal hypoxia, on MHC-I and CD3-ζ expression in the hippocampus. We show that there is a robust postnatal up-regulation of CD3-ζ and MHC-I protein as well as of MHC-I mRNA and that TNF-α down-regulates the expression of CD3-ζ protein and MHC-I mRNA in early postnatal but not in weanling nor in adolescent rats. These results may offer a molecular explanation to the adverse effects of increased circulating levels of cytokines on brain in neonatal hypoxia. Copyright © 2006 International Pediatric Research Foundation, Inc.