Effects of IL-1 and cortisol on beta-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells.
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.
Nakane
T
T
Laboratory of Physiologic and Pharmacologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892.
Szentendrei
T
T
Stern
L
L
Virmani
M
M
Seely
J
J
Kunos
G
G
D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D006131:Growth Inhibitors; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology* / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D006131:Growth Inhibitors; D007375:Interleukin-1; D011943:Receptors, Adrenergic, beta; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D000242:Cyclic AMP; D007545:Isoproterenol; D006854:Hydrocortisone