Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway
Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger mole...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/2012/748572 |
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| author | Takekatsu Saito Naotoshi Sugimoto Kunio Ohta Tohru Shimizu Kaori Ohtani Yuko Nakayama Taichi Nakamura Yashiaki Hitomi Hiroyuki Nakamura Shoichi Koizumi Akihiro Yachie |
| author_facet | Takekatsu Saito Naotoshi Sugimoto Kunio Ohta Tohru Shimizu Kaori Ohtani Yuko Nakayama Taichi Nakamura Yashiaki Hitomi Hiroyuki Nakamura Shoichi Koizumi Akihiro Yachie |
| author_sort | Takekatsu Saito |
| collection | DOAJ |
| description | Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling. |
| format | Article |
| id | doaj-art-e6c288f103794b56a96b9a8907fb4570 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-e6c288f103794b56a96b9a8907fb45702025-02-03T01:23:40ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/748572748572Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal PathwayTakekatsu Saito0Naotoshi Sugimoto1Kunio Ohta2Tohru Shimizu3Kaori Ohtani4Yuko Nakayama5Taichi Nakamura6Yashiaki Hitomi7Hiroyuki Nakamura8Shoichi Koizumi9Akihiro Yachie10Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Microbiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Microbiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Public Health, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Public Health, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanUnited Graduate School of Child Development, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanSpecific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling.http://dx.doi.org/10.1100/2012/748572 |
| spellingShingle | Takekatsu Saito Naotoshi Sugimoto Kunio Ohta Tohru Shimizu Kaori Ohtani Yuko Nakayama Taichi Nakamura Yashiaki Hitomi Hiroyuki Nakamura Shoichi Koizumi Akihiro Yachie Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway The Scientific World Journal |
| title | Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway |
| title_full | Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway |
| title_fullStr | Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway |
| title_full_unstemmed | Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway |
| title_short | Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway |
| title_sort | phosphodiesterase inhibitors suppress lactobacillus casei cell wall induced nf κb and mapk activations and cell proliferation through protein kinase a or exchange protein activated by camp dependent signal pathway |
| url | http://dx.doi.org/10.1100/2012/748572 |
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