Salbutamol increases tristetraprolin expression in macrophages

• Published in: Life sciences (1973) 2007-12, Vol.81 (25), p.1651-1658
• Main Authors: Jalonen, Ulla, Leppänen, Tiina, Kankaanranta, Hannu, Moilanen, Eeva
• Format: Article
• Language: English
• Subjects: Activator protein 2; Albuterol - pharmacology; Animals; Asthma; Blotting, Northern; Bucladesine - pharmacology; cAMP; Colforsin - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; Inflammation; Macrophages - metabolism; Mice; RNA Stability - drug effects; RNA-Binding Proteins - metabolism; Salbutamol; Tristetraprolin; Tristetraprolin - drug effects; Tristetraprolin - genetics; Tristetraprolin - metabolism; Tumor Necrosis Factor-alpha - metabolism; β 2-agonist
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2007.09.022

Tristetraprolin (TTP) is a tandem zinc finger protein that can bind to AU-rich elements (AREs) in the 3′-untranslated regions (3′-UTR) in mRNAs of transiently expressed genes, e.g. tumor necrosis factor-α (TNF-α) and granulocyte macrophage colony-stimulating factor (GM-CSF). TTP increases the turnover rate of the target mRNAs, thereby reducing, for example, the expression of TNF-α and GM-CSF. We examined the role of β 2-agonists, cAMP analogs, and forskolin (an activator of adenylate cyclase) on TTP mRNA and protein expression by quantitative real-time RT-PCR and Western blotting in J774 murine macrophages and THP-1 human macrophages. All of these agents increased TTP expression. A nonspecific inhibitor of phosphodiesterases (PDEs) 3-isobutyl-1-methylxanthine (IBMX) and type IV PDE-inhibitor rolipram further enhanced the increase in TTP expression levels, suggesting a cAMP-mediated effect. A possible mediator of these effects is transcription factor activator protein 2 (AP-2), whereas nuclear factor κB (NF-κB) seemed not to play any role. This mechanism may, at least in part, explain the anti-inflammatory effects which β 2-agonists have been reported to have in macrophages.