Open AccessA POSSIBLE ROLE OF GLUCOCORTICOIDS: AN INTRINSIC INHIBITOR OF THE CYTOTOXIC ACTIVITY OF TUMOR NECROSIS FACTOR
Author(s) -
Abe Shigeru,
Yamamoto Takahiko,
Iihara Seiji,
Yamazaki Masatoshi,
Mizuno Den'ichi
Publication year - 1988
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1988.tb01591.x
Subject(s) - cycloheximide , cytotoxic t cell , phospholipase a2 , tumor necrosis factor alpha , glucocorticoid , in vivo , mechanism of action , cytotoxicity , dexamethasone , endocrinology , medicine , phospholipase , dactinomycin , phospholipase a , in vitro , biology , chemistry , biochemistry , enzyme , protein biosynthesis , microbiology and biotechnology
The cytotoxic activity of tumor necrosis factor (TNF) against L929 fibroblasts in vivo was non‐competitively inhibited by physiological concentrations of glucocorticoids such as hydrocortisone (10 ‐7 M ), corticosterone (5 × 10 ‐8 M ) and dexamethasone (5 × 10 ‐9 M ). The inhibition was abolished by the addition of actinomycin D (0.5 μg/ml) or cycloheximide (4μ M ). A phospholipase A 2 inhibitor, quinacrine (2 × 10 ‐6 M ), also inhibited the TNF cytotoxicity. These findings suggest that the antitumor cytotoxic reaction by TNF is regulated by glucocorticoid through some mechanism involving de novo transcription and translation and that this regulatory mechanism may involve inhibition of phospholipase A 2 activity.