Document Detail

Inhibition of human B cell activation by diterpine forskolin: interference with B cell growth factor-induced G1 to S transition of the B cell cycle.
MedLine Citation:
PMID:  6086754     Owner:  NLM     Status:  MEDLINE    
We have previously demonstrated that a series of sequential steps are involved in the induction of a resting human B cell to proliferate. In this system, initial activation signals were delivered by either in vivo or in vitro stimulation, and proliferative signals were delivered by a B cell growth factor (BCGF) that was derived from a human T-T cell hybridoma. The involvement of adenosine 3',5'-monophosphate (cAMP) in regulating the growth and differentiation of lymphocytes has been of considerable interest. Diterpine forskolin has been reported to be a unique adenylate cyclase activator in membranes from mammalian tissues that results in elevations of intracytoplasmic cAMP. We have examined the effect of this drug on the progression of human B cells through their activation cycle. It was found that forskolin causes a rapid and sustained increase of cytoplasmic cAMP in purified small and large B cells. In the in vitro costimulation of small resting B cells with anti-mu plus BCGF, forskolin inhibited the proliferative response of B cells in a dose-dependent manner. This forskolin-mediated suppression of B cell proliferation was found when the drug was added to the cultures as late as 36 hr after initial stimulation. Of note is the fact that the anti-mu-induced RNA synthesis as well as cell enlargement in resting B cells was not inhibited by the addition of forskolin, whereas BCGF-induced proliferative response of activated B cells was markedly inhibited by the drug. Thus, these data demonstrate that forskolin, an agent that elevates cytoplasmic cAMP levels, has relatively little effect on early events in the human B cell cycle (G0 to G1) transition, but selectively inhibits the progression of BCGF-induced G1 to S phase transition of B cells.
A Muraguchi; K Miyazaki; J H Kehrl; A S Fauci
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  133     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1984 Sep 
Date Detail:
Created Date:  1984-09-18     Completed Date:  1984-09-18     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1283-7     Citation Subset:  AIM; IM    
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MeSH Terms
B-Lymphocytes / cytology,  immunology*,  metabolism
Cyclic AMP / metabolism
DNA / biosynthesis
Diterpenes / pharmacology*
Growth Inhibitors / pharmacology*
Growth Substances / pharmacology
Interphase / drug effects*
Lymphocyte Activation / drug effects*
Lymphokines / pharmacology
Reg. No./Substance:
0/Diterpenes; 0/Growth Inhibitors; 0/Growth Substances; 0/Lymphokines; 207137-56-2/Interleukin-4; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 9007-49-2/DNA

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