CELLULAR AND MOLECULAR EVENTS INVOLVED IN THE ANTI-TUMORAL EFFECT OF LIPOTEICHOIC ACID FROM LACTOBACILLUS RHAMNOSUS GG.

FRIEDRICH, A; CAMPO, V; MANUELLI, P; LEONI, J; PAZ, ML; GONZALEZ MAGLIO, D

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

In previous reports our lab has proved theanti-tumoral effect of orally administered lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) on an UltravioletB (UVB)-induced non-melanoma skin cancer mouse model. The aim of the present work was toevaluate underlying mechanisms involved in this anti-tumoral effect. We tested the modulatory capacity of orallyadministered LTA regarded to gene transcription in Peyer's patches (PP), smallintestine free from PP (SI) and mesenteric lymph nodes (MLN) by PCR. After asingle dose of 100 μg LTA the transcription of TNF-α, IL-10 and IL-1β in SI andIFN-g in PP was increased at 16hs. At 24 hs we observed a significant increase inTNF-α and IL-12p35 transcription in PP. Finally at 48 hs a significant increasein IFN-g transcription was observed in MLN. In order to evaluate the capacity of orallyadministered LTA to revert UVB-induced immunosuppression, we performed ahypersensitivity assay to oxazolone after a 12 dose treatment in irradiated andcontrol mice. We observed that UVB-irradiated and LTA-treated mice showed apartial reversion of immunosuppression after oxazolone challenge compared withirradiated and PBS-treated ones.At last, in order to evaluate the anti-tumoralcapacity of LTA in an UV-independent model, we tested a multiple doses scheduletreatment in animals that already had developed skin tumors but were no longerexposed to UVB irradiation. Animals with visible and multiple skin tumors were administeredwith LTA by gastric gavage every other day. We demonstrated that LTA is capableto significantly reduce the tumor number and total tumor area after 4 weeks oftreatment and that this reduction was abolished by the suspension of thetreatment. In conclusion, LTA from LGG has proven to produce several in vivo effects after one or multipleoral administrations. This could be useful to a better understanding of the interactionsbetween molecules isolated from probiotic bacteria and host immune response.