Growth hormone prevents Fas-induced apoptosis in lymphocytes through modulation of Bcl-2 and caspase-3.
OBJECTIVE
Growth hormone (GH) has been reported to have a potent effect on the immune system. However, the detailed mechanism of the effect of GH on the immune system has not yet been clarified. This study was designed to investigate the nature of this mechanism.


METHODS
In the present study, we investigated the effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM-9 lymphocytes to Fas-induced apoptosis.


RESULTS
Both cell lines expressed GH receptor mRNA. GH rescued Fas-induced suppression of [(3)H]-thymidine incorporation into each cell line. GH prevented Fas-induced apoptosis in each cell line without changing Fas antigen expression. We next investigated the mechanisms of the prevention of Fas-induced apoptosis, by focusing on intracellular molecules related to the apoptotic signal. Bcl-2 expression was increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also downregulated caspase-3 expression and inhibited activation of caspase-3 in both cell lines.


CONCLUSIONS
These findings suggest that GH regulates the human immune system through inhibition of Fas-induced apoptosis in activated T and B lymphocytes.
Mitsunaka
H
H
First Department of Internal Medicine, School of Medicine, Kagawa Medical University, Kita-gun, Kagawa, Japan. mitunaka@kms.ac.jp
Dobashi
H
H
Sato
M
M
Tanaka
T
T
Kitanaka
A
A
Yamaoka
G
G
Tokuda
M
M
Matoba
K
K
Hiraishi
T
T
Ishida
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004703:Endocrine System / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D013006:Growth Hormone / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D019014:fas Receptor; D013006:Growth Hormone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases