Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of anti-inflammatory molecules.
Glucocorticoids are well known for their anti-inflammatory effect through the regulation of gene expression in many types of immune cells, including mast cells. However, the genes that are involved in suppression of mast cell-mediated inflammation by glucocorticoids have not been fully identified. Therefore, we examined the dexamethasone (Dex)-responsive genes in RBL-2H3 mast cells using a high-density oligonucleotide microarray technique. Gene expression profiling revealed that the antigen-induced up-regulation of pro-inflammatory factors, including monocyte chemoattractant protein-1, was markedly inhibited by 100 nM Dex. On the other hand, Dex treatment itself caused the substantial up-regulation of many genes, including phenylethanolamine-N-methyl transferase (PNMT) and cytokine-inducible SH2-containing protein (CISH), in the mast cells. The expression of these two genes significantly increased 6 h after Dex exposure and lasted for more than 24 h. Considering that PNMT is the rate-determining enzyme in epinephrine synthesis and that CISH is a suppressor of cytokine signaling, these Dex-responsive genes may be potential anti-inflammatory factors. Thus, gene expression profiling suggested that Dex might exert its anti-inflammatory effect through two pathways in mast cells: the suppression and induction of potentially pro- and anti-inflammatory factors, respectively.
Nakamura
Ryosuke
R
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Okunuki
Haruyo
H
Ishida
Seiichi
S
Saito
Yoshiro
Y
Teshima
Reiko
R
Sawada
Jun-Ichi
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000941:Antigens / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D017874:Immediate-Early Proteins / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D050826:Suppressor of Cytokine Signaling Proteins
D000893:Anti-Inflammatory Agents; D000941:Antigens; D018932:Chemokine CCL2; D003907:Dexamethasone; D017874:Immediate-Early Proteins; D010625:Phenylethanolamine N-Methyltransferase; D012333:RNA, Messenger; D050826:Suppressor of Cytokine Signaling Proteins; C491766:Ccl2 protein, rat