Inhibition by dexamethasone of interleukin 13 production via glucocorticoid receptor-mediated inhibition of c-Jun phosphorylation.
The antigen stimulation of RBL-2H3 cells induced interleukin 13 (IL-13) production, which was inhibited by the steroidal anti-inflammatory drug dexamethasone and by the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Dexamethasone did not inhibit the antigen-induced phosphorylation of JNK but inhibited that of c-Jun. In a cell-free system, the phosphorylation of glutathione S-transferase-fused c-Jun by recombinant JNK was not inhibited by dexamethasone but was inhibited by the addition of recombinant glucocorticoid receptor (GR). These findings suggest that the inhibition of antigen-induced IL-13 production by dexamethasone is due to the GR-mediated inhibition of c-Jun phosphorylation induced by JNK.
Hirasawa
Noriyasu
N
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Izumi
Shinichiroh
S
Linwong
Watchara
W
Ohuchi
Kazuo
K
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004140:Dinitrophenols / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000494:pharmacology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism
D000873:Anthracenes; D004140:Dinitrophenols; D018793:Interleukin-13; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D018808:Transcription Factor AP-1; C432165:pyrazolanthrone; D007073:Immunoglobulin E; D003907:Dexamethasone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases