Pharmacological modulation of c-fos mRNA expression in the HL60 and U937 cell lines.
A variety of drugs known to act via increasing intracellular cAMP are used in the treatment of asthma. In this study we asked whether anti-asthma drugs are capable of altering gene activation. We determined whether phosphodiesterase inhibitors, either alone or in combination with adrenoceptor agonists, were able to alter the abundance of mRNA of the cAMP responsive gene c-fos in the cell-lines HL60 and U937. Incubation of cells with phosphodiesterase inhibitors aminophylline, theophylline or pentoxyphylline all resulted in an increase in c-fos mRNA. Further upregulation of c-fos mRNA abundance was observed when the cells were stimulated with the combination of aminophylline and adrenoceptor agonists with beta 2-agonist activity. These increases in c-fos mRNA were accompanied by increases in intracellular concentration of cAMP. These data suggest that in these in vitro models, combinations of beta 2-adrenoceptor agonists and phosphodiesterase inhibitors can increase intracellular cAMP and affect gene activation.
Kotecha
S
S
St Mary's Hospital Medical School, London, UK.
Wilson
L
L
Sutcliffe
S
S
Wangoo
A
A
Shaw
R J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics*; D006644:Histiocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics*; D013268:Stimulation, Chemical; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D000628:Aminophylline; D003994:Bucladesine; D007545:Isoproterenol