Rapid induction of REDD1 gene expression in macrophages in response to stress-related catecholamines

• REDD1 is characterized as a new host defense factor.
• We examined effect of adrenaline and noradrenaline on macrophage expression of REDD1.
• Adrenaline and noradrenaline upregulated REDD1 expression in macrophages.
• β2-Adrenoceptor and cAMP appeared to be responsible for the REDD1 upregulation.

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.