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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1984-9-18
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1283-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
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.
pubmed:publicationType
Journal Article