Cellular and molecular events involved in the anti-tumoral effect of lipoteichoic acid from Lactobacillus rhamnsosus GG

FRIEDRICH ADRIAN; CAMPO, VALERIA; MANUELLI, PAULA; LEONI, JULIANA; PAZ, MARIELA; GONZÁLEZ MAGLIO, DANIEL

Encuentro; Reunión Anual SAI- SAIC-SAFE; 2016

SAI-SAFE

In previous reports our lab has proved the anti-tumoral role of orally administered lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) in mice exposed to UVB chronic irradiation. In relation to this, the aim of the present work is to evaluate the mechanisms involved in this effect. We tested the modulation capacity of orally administered LTA regarded to gene transcription in gut associated lymphoid tissue such as Peyer´s patches (PP), small intestine free from PP (SI) and mesenteric lymph nodes (MLN) by PCR. After a single dose of 100 ug LTA the transcription of TNF-α, IL-10 and IL-1β in SI and IFN-g in PP were increased at 16hs. At 24 hs we observed a significant increase in TNF- α and IL-12p35 transcription in PP. Finally at 48 hs a significant increase in IFN-g transcription was observed in MLN. In order to evaluated the capacity of orally administered LTA to reverse UVB immunosuppression we performed a CHS assay with oxazolone after a 12 dose treatment. We observed that UVB-irradiated and LTA-treated mice showed a partial reversion after oxazolone challenge compared with irradiated and PBS-treated ones and non-irradiated controls.At last, in order to evaluate the anti-tumoral capacity of LTA in an UV-independent model, we tested a multiple doses schedule treatment in animals that already had developed skin tumors but were no longer exposed to UVB irradiation. Animals with visible and multiple skin tumors were administered with LTA by gastric gavage every other day. We demonstrated that LTA in capable to significantly reduce the tumor number and total tumor area after 4 weeks of treatment and that this reduction was abolished by the suspension of the treatment. In conclusion, LTA from LGG has proven to produce several in vivo effect after one or multiple oral administrations. This could be useful to a better understanding of the interactions between molecules isolated from probiotic bacteria and host immune response.