Human tumour-induced inhibition of interferon action in vitro: reversal of inhibition by beta-carotene (pro-vitamin A).
Inhibitors of human interferon action that might be relevant to tumour resistance or escape mechanisms were investigated in a macrophage system. The effects of IFN on macrophage Fc gamma receptor expression were inhibited by three preparations: (1) a low-molecular-weight component of normal autologous serum; (2) a low-molecular-weight component of carcinoma supernatant; and (3) physiological concentrations of retinol and retinoic acid. Since human carcinoma tissue contains abnormally high levels of retinoic acid-binding protein, the possibility that a tumour-associated retinoid contributes to tumour-induced inhibition in vitro was investigated. Inhibition of IFN action in vitro by retinoic acid (vitamin A acid) was found to be reversed by beta-carotene (pro-vitamin A). When tested in the tumour system beta-carotene also reversed inhibition by the human-carcinoma-derived signal. These data are consistent with the view that at least one of the tumour-derived signals inhibitory towards IFN is a tumour-associated retinoid, although firm evidence for this must await further physicochemical characterization of the inhibitory signal(s). The present data clearly show, nevertheless, that human tumour-induced inhibition of IFN in vitro can be reversed by the pro-vitamin beta-carotene.
D002338:Carotenoids / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000276:immunology; D011961:Receptors, Fc / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000276:immunology*; D019207:beta Carotene
D007370:Interferon Type I; D011961:Receptors, Fc; D019207:beta Carotene; D002338:Carotenoids