Cyclic AMP-mediated modulation of immunoglobulin production in B cells by prostaglandin E1.
We had previously demonstrated in a transformed human B cell line, LA350, the existence of an inverse relationship between cyclic adenosine monophosphate (cAMP) content and immunoglobulin secretion using the cAMP-elevating agents such as cholera toxin and forskolin. In this paper we report that cAMP acting as a second messenger for prostaglandin exerts a similar effect on the antibody response of B lymphocytes. Incubation of the cells with PGE1 in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) produced a concentration- and time-dependent elevation of intracellular cAMP. Significant increases of cAMP production were observed at physiologically relevant levels of PGE1 (10(-7) and 10(-8) M). Immunoglobulin production, whether measured as the total number of immunoglobulin-secreting cells by a reverse hemolytic plaque assay or as specific immunoglobulin production (IgM) by an enzyme-linked immunoadsorbent assay, was suppressed in a dose-dependent fashion by the presence of IBMX. This suppression of immunoglobulin production was significantly enhanced by the presence of PGE1. Phorbol myristate acetate-induced IgM production was also inhibited by the presence of PGE1. These results imply that prostaglandins regulate B cell activation and immunoglobulin production by signal transduction mechanisms involving cyclic nucleotides.
Patke
C L
CL
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Orson
F M
FM
Shearer
W T
WT
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007075:Immunoglobulin M; D007136:Immunoglobulins; D015237:Dinoprost; D000242:Cyclic AMP; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine