Regulation of interleukin 6 expression in murine bone marrow stromal cells.
The regulation of interleukin 6 (IL-6) expression in the B-lymphocyte-supporting murine stromal cell line BMS2 has been examined in response to exogenous cytokines and chemical agents. Kinetic analyses of IL-6 mRNA induction and decay are presented together with analysis of the IL-6 biological activity. The cytokines tumor necrosis factor, interleukin 1 (alpha and beta), and transforming growth factor beta, as well as forskolin and dibutyryl cyclic AMP, all induce a transient rise in the steady-state level of IL-6 mRNA and an increased release of IL-6 protein. To study its regulation at the chromatin level, the murine IL-6 genomic gene has been cloned. Induction of IL-6 expression correlates with increased DNA nicking, consistent with increased topoisomerase I and endogenous nuclease activity. This finding is supported by kinetic analyses using camptothecin, a topoisomerase I inhibitor. We conclude that IL-6 regulation in murine stromal cells capable of supporting B-lymphopoiesis is comparable to that observed in human diploid fibroblasts.
Gimble
J M
JM
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Hudson
J
J
Henthorn
J
J
Hua
X X
XX
Burstein
S A
SA
D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D003994:Bucladesine / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006207:Half-Life; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D003994:Bucladesine; D004247:DNA; D002166:Camptothecin