Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors.
In this report we demonstrate that retinoic acid (RA) down-regulated the number of IL-6R on human leukocyte cell lines, including the myeloma cell line AF10, and two B cell hybridomas that correspond to cells at earlier stages of B cell development. Using AF10 cells, whose growth was determined to be mediated by the autocrine action of IL-6, we found that RA reduction of IL-6R was concentration-dependent over a range of 10(-11) to 10(-5) M and corresponded to the ability of the retinoid to inhibit cell proliferation. The down-regulation of IL-6R number by RA was accompanied by reduced IL-6R mRNA expression. RA did not affect endogeneous IL-6 synthesis or secretion from AF10 cells. However, addition of exogenous rIL-6 could overcome RA-induced growth inhibition. Menthol, a structurally unrelated compound to RA, also suppressed IL-6R expression and, correspondingly, inhibited cell growth. Taken together, our results suggest that the antiproliferative action of RA on AF10 cells is caused by reduction of IL-6R expression and subsequent inhibition of IL-6-mediated autocrine growth. These findings suggest the possibility that down-regulation of IL-6R is a means by which RA can modulate immune function.
Sidell
N
N
Department of Pathology, UCLA School of Medicine 90024.
Taga
T
T
Hirano
T
T
Kishimoto
T
T
Saxon
A
A
D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008610:Menthol / Q000494:pharmacology; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011971:Receptors, Immunologic / Q000502:physiology*; D019947:Receptors, Interleukin-6; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D008610:Menthol; D014212:Tretinoin