Modification of glucocorticoid sensitivity by MAP kinase signaling pathways in glucocorticoid-induced T-cell apoptosis.
OBJECTIVE
Glucocorticoid is widely used for the treatment of diseases such as hematological malignancies. Glucocorticoid sensitivity is different from person to person and the mechanism of the regulation of glucocorticoid sensitivity is not well known. Glucocorticoid resistance is a major clinical problem.


RESULTS
Here, using glucocorticoid-induced T-cell apoptosis, a model system for the analysis of the mechanism of glucocorticoid action, we clarified that mitogen-activated protein kinases (MAPKs) modify glucocorticoid sensitivity, namely that the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase reduce and enhance glucocorticoid sensitivity, respectively.


CONCLUSIONS
These findings might provide new tools for overcoming glucocorticoid-resistance.
Tanaka
Tomoko
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Okabe
Taijiro
T
Gondo
Shigeki
S
Fukuda
Mitsue
M
Yamamoto
Masahiro
M
Umemura
Tsukuru
T
Tani
Kenzaburo
K
Nomura
Masatoshi
M
Goto
Kiminobu
K
Yanase
Toshihiko
T
Nawata
Hajime
H
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D002070:Butadienes; D005938:Glucocorticoids; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580