Comparative Responsiveness of HL-60, HL-60R, and HL-60R+ (LRARSN) Cells to Retinoic Acid, Calcitriol, 9 cis-Retinoic Acid, and Sodium Butyrate

In HL-60 cells, retinoic acid (RA) and 9 cis-RA induce granulocytic differentiation, and calcitriol and sodium butyrate induce monocytic differentiation. To study the role of retinoid resistance on the response to these agents, we investigated their effects in HL-60 cells, retinoid-resistant HL-60R cells, and HL-GOR+ cells in which retinoid sensitivity has been restored. In HL-60 cells, cathepsin D (ctsdj mRNA levels are increased by these agents and by cholera toxin after pretreatment with each agent. Calcitriol, 9 cis-RA, and sodium butyrate increase interleukin-8 (IL-8) mRNA expression, and pretreatment with these agents or RA potentiates the stimulation of IL-8 by phorbol ester ITPA). Pretreatment of HL-60 cells with all of the agents confers inducibility of cathepsin L ( c t s l l mRNA by TPA in previously unresponsive cells. In HL-60R cells, none of the agents alone or in combination significantly enhances the expression of the ctsd, IL-8, or ctsl mRNAs. Retinoid stimulation (either alone or in combination