title: Rapid induction of REDD1 gene expression in macrophages in response to stress-related catecholamines.
abstract: In the present study, we examined the effect of stress-related catecholamines adrenaline and noradrenaline on macrophage expression of a new host defense factor REDD1 using murine macrophage cell line RAW264.7 and murine peritoneal macrophages. Short-term adrenaline exposure (15-60 min) upregulated REDD1 mRNA expression and its protein synthesis in macrophages. This adrenaline-induced REDD1 expression was completely blocked by β2-adrenoceptor selective antagonist ICI 118,551, whereas β2-adrenoceptor specific agonist salmeterol markedly enhanced REDD1 expression. Moreover, noradrenaline increased REDD1 mRNA expression at doses higher than the effective doses of adrenaline. The effect of adrenaline on REDD1 mRNA expression was mimicked by treatment with membrane-permeable cAMP analog 8-Br-cAMP. Thus, increased intracellular cAMP level resulting from β2-adrenoceptor stimulation appeared to be responsible for adrenaline-induced REDD1 mRNA expression. However, inhibiting protein kinase A (PKA) activity had no significant effect on REDD1 mRNA expression after β2-adrenoceptor stimulation. In addition, exchange protein activated by cAMP (Epac) agonist 8-CPT-20-O-Me-cAMP had no effect on REDD1 mRNA expression. Thus, β2-adrenoceptor-mediated increase in cAMP levels seems to induce REDD1 mRNA expression in macrophages through a PKA- and Epac-independent pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan. Electronic address: yanagawa@hoku-iryo-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hiraide
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; C469992:Ddit4 protein, mouse; C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014157:Transcription Factors; C026777:ICI 118551; D000068299:Salmeterol Xinafoate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000420:Albuterol; D009638:Norepinephrine; D004837:Epinephrine
keywords: Catecholamines; Macrophages; REDD1; β(2)-Adrenoceptor