MSH RECEPTORS AND THE RESPONSE OF HUMAN A375 MELANOMA-CELLS TO INTERLEUKIN-1-BETA

alpha-Melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) h as been shown to be an inhibitory factor in many immunologic and infla mmatory processes involving the cytokine interleukin-l (IL-1). As the mechanism of the interaction between IL-1 and alpha-MSH at the recepto r level is unknown, we have studied the role of MC1 melanocortin recep tors in two variants of the human melanoma cell line A375 differing in their sensitivity to the cytostatic effects of IL-1 beta. Both IL-1 s ensitive (A375r-) and resistant cells (A375r+) carry specific high aff inity receptors for IL-1, albeit their concentration is 10-fold higher in A375r+ cells. In A375r- cells, MCl receptors are absent or below t he level for reliable detection in the binding assay. Conversion of A3 75r- to A375r+ cells by prolonged culture in medium not depleted of en dotoxin led to the appearance of MCl receptors (K-D 0.4 +/- 0.123 nmol /l; 608 +/- 134 receptors/cell). Stable transfection of A375r- cells w ith the human MC1 receptor did not, however, render them resistant to the cytostatic effect of IL-1 beta on concomitant treatment with alpha -MSH or result in the production of IL-6 on treatment with IL-1 beta. Therefore, the presence of MC1 receptors on the surface of A375 cells or their binding to alpha-MSH does not seem to be a factor in cytokine resistance or IL-6 secretion. No interaction between IL-1 beta and al pha-MSH could be demonstrated at the cellular level in this melanoma c ell line.