EXPRESSION OF AH RECEPTOR (TCDD RECEPTOR) DURING HUMAN MONOCYTIC DIFFERENTIATION

We have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals. In this paper , the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined togethe r with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in prom yelocytic HL60 cells and erythroblastic HEL cells. However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts. Furthermore, a specific induction of AhR during mo nocytic differentiation was investigated in HL60 and HEL cells. HL60 c ells were induced to differentiate toward monocytes-macrophages by inc ubation with phorbol ester, showing a 5- to 20-fold increase of AhR mR NA. The incubation with transforming growth factor beta 1 and 1 alpha, 25-dihydroxyvitamin D-3 resulted in a 5- to 7-fold increase of AhR mRN A. The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by thes e combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types. Tr eatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene. These resul ts indicated that expression of AhR mRNA was significantly induced dur ing monocytic differentiation and that the differentiated cells were r esponsive to xenobiotics. Our results suggest that AhR may play an imp ortant role in the function of monocytes and also in the eventual acti vation of environmental carcinogens.