Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation
The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H 2 receptors showed a rapid,...
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todo:paper_00142999_v350_n1_p121_Brodsky2023-10-03T14:12:05Z Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation Brodsky, A. Davio, C. Shayo, C. Legnazzi, B.L. Barbosa, M. Lardo, M. Morelli, A. Baldi, A. Avalos, J.C.S. Rivera, E. CAMP Cell differentiation Desensitization Forskolin Histamine U937 cell complement component C5a cyclic AMP dimaprit forskolin histamine histamine H2 receptor Myc protein antigen expression article cell differentiation cell level cell line cell proliferation chemotaxis concentration response controlled study dose response drug effect growth inhibition priority journal receptor down regulation receptor occupancy respiratory burst Antigens, Neoplasm Cell Differentiation Cell Division Cell Line Chemotaxis Cyclic AMP Dose-Response Relationship, Drug Forskolin Genes, myc Histamine Humans Oxidation-Reduction Tumor Cells, Cultured The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H 2 receptors showed a rapid, homologous desensitization, which might explain the dissimilar responses to histamine and dbcAMP. Forskolin induced an increase in cAMP levels in a concentration-dependent manner (EC 50 = 30 μM) for an extended period of at least 24 h. Forskolin but not histamine (up to 100 μM), also inhibited cell growth in a dose-dependent fashion (EC 50 = 22 μM). After 3 days of incubation, 75 μM forskolin induced U937 cell differentiation as judged by an increased rate of reduction of nitrobluetetrazolium (mean ± S.E.M.: 21.3 ± 6.6% in treated cells vs. 3.2 ± 1.9% in the control group, P < 0.001) and an augmented chemotactic response to complement 5a (C5a) (33.2 ± 5.9% in forskolin-treated vs. 0.34 ± 0.12% in control cells, P < 0.01). Furthermore, c-Myc levels decreased following forskolin treatment, while the histamine H2 receptor agonist dimaprit had no effect. We conclude that forskolin induces U937 cell differentiation through a sustained rise in cAMP levels. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00142999_v350_n1_p121_Brodsky |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CAMP Cell differentiation Desensitization Forskolin Histamine U937 cell complement component C5a cyclic AMP dimaprit forskolin histamine histamine H2 receptor Myc protein antigen expression article cell differentiation cell level cell line cell proliferation chemotaxis concentration response controlled study dose response drug effect growth inhibition priority journal receptor down regulation receptor occupancy respiratory burst Antigens, Neoplasm Cell Differentiation Cell Division Cell Line Chemotaxis Cyclic AMP Dose-Response Relationship, Drug Forskolin Genes, myc Histamine Humans Oxidation-Reduction Tumor Cells, Cultured |
| spellingShingle |
CAMP Cell differentiation Desensitization Forskolin Histamine U937 cell complement component C5a cyclic AMP dimaprit forskolin histamine histamine H2 receptor Myc protein antigen expression article cell differentiation cell level cell line cell proliferation chemotaxis concentration response controlled study dose response drug effect growth inhibition priority journal receptor down regulation receptor occupancy respiratory burst Antigens, Neoplasm Cell Differentiation Cell Division Cell Line Chemotaxis Cyclic AMP Dose-Response Relationship, Drug Forskolin Genes, myc Histamine Humans Oxidation-Reduction Tumor Cells, Cultured Brodsky, A. Davio, C. Shayo, C. Legnazzi, B.L. Barbosa, M. Lardo, M. Morelli, A. Baldi, A. Avalos, J.C.S. Rivera, E. Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| topic_facet |
CAMP Cell differentiation Desensitization Forskolin Histamine U937 cell complement component C5a cyclic AMP dimaprit forskolin histamine histamine H2 receptor Myc protein antigen expression article cell differentiation cell level cell line cell proliferation chemotaxis concentration response controlled study dose response drug effect growth inhibition priority journal receptor down regulation receptor occupancy respiratory burst Antigens, Neoplasm Cell Differentiation Cell Division Cell Line Chemotaxis Cyclic AMP Dose-Response Relationship, Drug Forskolin Genes, myc Histamine Humans Oxidation-Reduction Tumor Cells, Cultured |
| description |
The present study examines the effects of forskolin on U937 cell differentiation. We recently reported that dibutyryl cAMP (dbcAMP), but not cAMP-elevating agents such as histamine, promotes U937 cell differentiation. cAMP production elicited by stimulation of histamine H 2 receptors showed a rapid, homologous desensitization, which might explain the dissimilar responses to histamine and dbcAMP. Forskolin induced an increase in cAMP levels in a concentration-dependent manner (EC 50 = 30 μM) for an extended period of at least 24 h. Forskolin but not histamine (up to 100 μM), also inhibited cell growth in a dose-dependent fashion (EC 50 = 22 μM). After 3 days of incubation, 75 μM forskolin induced U937 cell differentiation as judged by an increased rate of reduction of nitrobluetetrazolium (mean ± S.E.M.: 21.3 ± 6.6% in treated cells vs. 3.2 ± 1.9% in the control group, P < 0.001) and an augmented chemotactic response to complement 5a (C5a) (33.2 ± 5.9% in forskolin-treated vs. 0.34 ± 0.12% in control cells, P < 0.01). Furthermore, c-Myc levels decreased following forskolin treatment, while the histamine H2 receptor agonist dimaprit had no effect. We conclude that forskolin induces U937 cell differentiation through a sustained rise in cAMP levels. |
| format |
JOUR |
| author |
Brodsky, A. Davio, C. Shayo, C. Legnazzi, B.L. Barbosa, M. Lardo, M. Morelli, A. Baldi, A. Avalos, J.C.S. Rivera, E. |
| author_facet |
Brodsky, A. Davio, C. Shayo, C. Legnazzi, B.L. Barbosa, M. Lardo, M. Morelli, A. Baldi, A. Avalos, J.C.S. Rivera, E. |
| author_sort |
Brodsky, A. |
| title |
Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| title_short |
Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| title_full |
Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| title_fullStr |
Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| title_full_unstemmed |
Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation |
| title_sort |
forskolin induces u937 cell line differentiation as a result of a sustained camp elevation |
| url |
http://hdl.handle.net/20.500.12110/paper_00142999_v350_n1_p121_Brodsky |
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