Different effect of prostaglandin E2 on B-cell activation by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2: selective inhibition of B151-TRF2-induced antibody response through increases in intracellular cyclic AMP levels.
Effects of prostaglandin E2 (PGE2) on murine B-cell activation induced by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2, were examined. A final differentiation of unprimed B cells into IgM-producing cells induced by B151-TRF2 was markedly inhibited by PGE2 at physiological concentrations (around 10(-8) M), whereas B151-TRF1/IL-5- induced antibody responses of unprimed as well as activated B cells were not affected by PGE2, even at 10(-6) M. B-cell responses induced by B151-TRF2-like factors from autoimmune-prone MRL/lpr mice were also inhibited by PGE2. Biphasic increases in intracellular cyclic AMP (cAMP) levels were induced by culturing B cells with 10(-6) or 10(-8) M PGE2: rapid increases within 8 min and delayed increases around 16 hr. The direct addition of dibutyryl cAMP to cultures of B cells resulted in marked inhibition of antibody responses when stimulated with B151-TRF2 but not with B151-TRF1/IL-5. The B151-TRF2-induced antibody responses were also inhibited by cAMP-elevating reagents such as forskolin, cholera toxin and theophylline. Furthermore, 2'.5'-dideoxyadenosine, which is an inhibitor of adenylate cyclase, prevented the PGE2-mediated cAMP accumulation in unprimed B cells as well as the PGE2-mediated inhibition of B151-TRF2-induced B-cell responses when added at the initiation of culture. These results suggest that PGE2 inhibits B151-TRF2-induced antibody responses through the activation of adenylate cyclase and subsequent accumulation of intracellular cAMP, whereas B151-TRF1/IL-5-responsive B cells are resistant to the inhibitory effect of PGE2 and cAMP.
Ishihara
K
K
Division of Oncogenesis, Osaka University Medical School, Japan.
Ono
S
S
Takahama
Y
Y
Hirayama
F
F
Hirano
H
H
Itoh
K
K
Dobashi
K
K
Murakami
S
S
Katoh
Y
Y
Yamaguchi
M
M
D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000494:pharmacology / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice
D000276:Adjuvants, Immunologic; D007075:Immunoglobulin M; D015848:Interleukin-5; D015847:Interleukin-4; D016048:Dideoxyadenosine; D003994:Bucladesine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D015232:Dinoprostone