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

Abstract EN

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.