Effect of TNF-alpha on CD3-zeta and MHC-I in postnatal rat hippocampus.
The zeta 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-zeta expression in hippocampus from early postnatal, weanling and adolescent rats and to record the effects of TNF-alpha and IL-1beta, cytokines commonly increased in neonatal hypoxia, on MHC-I and CD3-zeta expression in the hippocampus. We show that there is a robust postnatal up-regulation of CD3-zeta and MHC-I protein as well as of MHC-I mRNA and that TNF-alpha down-regulates the expression of CD3-zeta 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.
Sourial-Bassillious
Nermin
N
Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, SE-171 76 Stockholm, Sweden. nermin.bassillious@ki.se
Eklöf
Ann-Christine
AC
Scott
Lena
L
Aperia
Anita
A
Zelenin
Sergey
S
D000818:Animals; D017252:CD3 Complex / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015395:Histocompatibility Antigens Class I; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha