The Journal of Immunology, Vol 145, Issue 1 260-266, Copyright © 1990 by American Association of Immunologists

ARTICLES

Effects of IL-1 and cortisol on beta-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells

T Nakane, T Szentendrei, L Stern, M Virmani, J Seely and G Kunos
Laboratory of Physiologic and Pharmacologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892.

The effects of IL-1 and cortisol, and their interactions on the density of beta-adrenergic receptors (beta AR), cell proliferation, and the adherence of cells to plastic were studied in cultured human A549 lung tumor cells. The density of beta AR, assayed by 125I-pindolol binding, was increased two- to threefold by a 24-h incubation of the cells with IL-1 alpha, IL-1 beta, and TNF-alpha (EC50: 2.7, 8.2, and 24 pM, respectively), although a series of other cytokines and growth factors did not have this effect. Cortisol also increased beta AR density (EC50: 30 nM) and markedly potentiated the effects of IL-1 alpha, IL-1 beta, and TNF-alpha. Neither IL-1 nor cortisol influenced the proportion of cell surface vs internalized beta AR. The IL-1-induced increase in beta AR density was half-maximal after 6 h, was reversible at a similar rate, and was blocked by 1 microM of cycloheximide. The effect of IL-1 on beta AR was specific, as the density of glucocorticoid receptors, measured by 3H-dexamethasone binding, was reduced by IL-1. Both cortisol and IL-1 potentiated the isoproterenol- induced increase in cAMP accumulation. IL-1 inhibited cell proliferation and thymidine uptake, and increased the adherence of A549 cells to the plastic culture flask, as quantified by a cell detachment assay. The effect of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol decreased cell adherence and prevented the IL-1- induced increase in adherence. The results indicate that multiple effects of IL-1 in a cultured tumor cell line involve different mechanisms, suggesting heterogeneity of IL-1R and/or coupling of IL-1R to distinct, nuclear, and nonnuclear, effector pathways.

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