Ca2+ signaling down-regulates TGF-beta1 gene expression in CD4+ T cells.
In the immune system, TGF-beta1 exerts two major functions, anti-inflammatory and immuno-suppressive effects. This work aims to investigate the molecular mechanisms involved in the regulation of the TGF-beta1 gene expression in CD4(+) T cells. The TGF-beta1 gene expresses three transcripts of 2.5, 1.9, and 1.4kb. The 1.9kb mRNA which has the highest translation activity was the major transcript. The relationship between T cell receptor (TCR) stimulation and the expression of the gene was investigated. TCR stimulation with a low dose of antigen peptide enhanced the gene expression, whereas a higher dose suppressed the expression. TCR stimulation activates PKC/MAPK and Ca(2+) signaling pathways. PMA increased the gene expression, whereas ionomycin decreased the gene expression, markedly. The results indicate that Ca(2+) signaling down-regulates TGF-beta1 gene expression. The molecular regulation of TGF-beta1 gene expression is unique when comparing to other cytokine genes which are generally activated by Ca(2+) signaling.
Kohyama
Masako
M
Research Institute for Biological Sciences, Tokyo University of Science (RIKADAI), 2669 Yamazaki, Noda, Chiba-ken 278-0022, Japan.
Yasogi
Yasuhito
Y
Nakano
Naoko
N
Ise
Wataru
W
Kaminogawa
Shuichi
S
Hozumi
Nobumichi
N
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D017635:Clonal Anergy; D015536:Down-Regulation / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D000941:Antigens; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1