title: Enhanced transglutaminase 2 expression in response to stress-related catecholamines in macrophages.
abstract: Transglutaminase 2 (TG2) is a multifunctional protein that contributes to inflammatory disease when aberrantly expressed. Although macrophages express TG2, the factor stimulating TG2 expression remains poorly characterized in these cells. In the present study, we examined the effects of the stress-related catecholamines adrenaline and noradrenaline on macrophage expression of TG2 in RAW264.7 murine macrophages and murine bone marrow-derived macrophages. Treatment with adrenaline markedly increased TG2 mRNA expression and increased TG2 protein levels. While the β2-adrenoceptor-selective antagonist ICI 118,551 completely blocked adrenaline-induced TG2 mRNA expression, the β2-adrenoceptor specific agonist salmeterol increased TG2 expression. Noradrenaline also increased TG2 mRNA expression at higher doses than the effective doses of adrenaline. The effect of adrenaline on TG2 mRNA expression was mimicked by treatment with the membrane-permeable cAMP analog 8-Br-cAMP. Thus, increased intracellular cAMP following stimulation of β2-adrenoceptors appeared to be responsible for adrenaline-induced TG2 expression. Because stress events activate the sympathetic nervous system and result in secretion of the catecholamines, adrenoceptor-mediated increase in macrophage TG2 expression might be associated with stress-related inflammatory disorders.
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: Kei-Ichi
authors.initials: K
authors.lastname: Shimamura
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: D000818:Animals; D002478:Cells, Cultured; D004837:Epinephrine / Q000378:metabolism* / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D015151:Immunoblotting; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000276:immunology*; D011503:Transglutaminases / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D009638:Norepinephrine; D004837:Epinephrine
keywords: Adrenaline; Macrophages; Transglutaminase 2; cAMP; β(2)-Adrenoceptor