All-trans Retinoic Acid Induces Expression and Secretion of Carboxypeptidase D in THP-1 Cells

Abstract

Carboxypeptidase D (CPD) is a zinc-dependent protease, which is highly expressed in macrophages, and is thought to participate in inflammatory processes. In the present study, we investigated the possible regulatory effect of all-trans retinoic acid (ATRA), which is an active form of vitamin A and plays a critical regulatory role in both the innate and adaptive immunity, on CPD expression and secretion in human monocytic THP-1 cells. CPD mRNA expression first increased, from a concentration as low as 10 nM ATRA to a maximum level of expression, at 1 μM. ATRA enhanced intracellular CPD expression in a time- and concentration-dependent manner but did not affect cell surface CPD expression. Interestingly, 9-cis-RA did not affect CPD expression. Additionally, an experiment with RAR/RXR selective agonist or antagonists demonstrated that ATRA-induced enhancement of CPD expression was RAR/RXR dependent. ATRA also enhanced CPD secretion from THP-1 cells; however, this enhancement was RAR/RXR-independent. The anti-inflammatory agent dexamethasone reversed ATRA-induced enhancement of CPD expression and secretion. Our results suggest ATRA exerts regulatory effects on expression and secretion of CPD in human monocytes, and ATRA-induced CPD secretion may be associated with inflammatory response.