Modulation of glucocorticosteroid binding in human lymphoid, monocytoid and hepatoma cell lines by inflammatory cytokines interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha.
In order to elucidate the role of the inflammatory cytokines in regulating glucocorticosteroid binding (GCSB) and glucocorticosteroid receptor (GR) level we incubated a B-cell line (CESS), a promonocytic cell line (U937) and a hepatoma cell line (HepG2) in the presence of varying concentrations of IL-1 beta, IL-6 and TNF-alpha for 24 h. Glucocorticosteroid binding was determined by the method of 'whole cell uptake', and the cellular appearance of the glucocorticosteroid receptor was detected by immunocytochemistry. A rise in the glucocorticosteroid binding was induced by all three cytokines. The increase in level of glucocorticosteroid receptors in the cells shown by immunocytochemistry was much more pronounced. However, antagonistic effects were demonstrated by both methods between IL-6 and TNF-alpha, and between IL-1 beta and TNF-alpha when they were applied simultaneously, in U937. Present data suggest that local imbalance in the ratio of these three cytokines in different pathological cases might influence the glucocorticosteroid sensitivity of the lymphocytes, monocytes and hepatocytes as target cells.
Rakasz
E
E
Department of Molecular Biology, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary.
Gal
A
A
Biró
J
J
Balas
G
G
Falus
A
A
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha