SIGNALING PATHWAYS INVOLVED IN TNF-á INHIBITION IN PBMC BY Lactobacillus reuteri

MECHOUD MONICA; MATEOS MELINA; SALVADOR GABRIELA; FONT DE VALDEZ, GRACIELA; RODRIGUEZ VIRGINIA

Puerto Madryn

Congreso; XLVI Reunion Anual de SAIB; 2010

SAIB

signaling pathways involved in TNF-α inhibition in PBMC by Lactobacillus reuteri   Mechoud MA1, Mateos MV2, Salvador GA2, Font de Valdez G1, Rodriguez AV1 1CERELA-CONICET. Tucumán. 2INIBIBB-CONICET. Bahía Blanca. Argentina. E-mail: mmechoud@cerela.org.ar   Lactobacillus strains have the capacity to modify cytokines production in different cells. However, the molecular mechanisms involved in this effect are not yet well understood. Previous investigations in our laboratory showed that L. reuteri CRL 1098 reduced TNF-α production in human peripheral blood mononuclear cells (PBMC), and this effect depended on membrane rafts integrity. The aim of this work was to investigate the signaling pathways involved in the decreased TNF-α production induced by L. reuteri CRL 1098 in PBMC. Using Western blot techniques it was demonstrated that when PBMC were co-incubated with L. reuteri cell-free supernatant, Lck protein migrated from rafts to non-rafts regions of the membrane. Also, different signaling proteins were modified after the incubation with the bacterial supernatant: increased levels of PI3K, pERK ½, and p-p38 were observed. Citoplasmic fraction of p65 NF-κB decreased while nuclear fraction of p65 NF-κB increased, indicating that this transcription factor could be partially responsible for TNF-α diminution. We postulate that L. reuteri could interfere with the ability of NF-kB to bind to DNA targets. These results provide clues to understand the mechanisms by which L. reuteri reduces TNF-α production in PBMC and demonstrate for the first time, interaction between a non-pathogenic bacterium and rafts.