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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   κ  B (NF-  κ  B) 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-  κ  B and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-  κ  B inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-  κ  B 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.

the scientific world journal/thescientificworldjournal

Phosphodiesterase Inhibitors Suppress<i>Lactobacillus casei</i>Cell-Wall-Induced NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="bold">κ</mml:mi></mml:math>B and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway

Phosphodiesterase Inhibitors SuppressLactobacillus caseiCell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A—or Exchange Protein Activated by cAMP-Dependent Signal Pathway