Efeito da administração oral de butirato de sódio na colite ulcerativa induzida por DSS em animais C57BL/6 e deficientes para TLR4: caracterização clínica, histopatológicas e de células do sistema imune

Abstract

Intestinal inflammatory diseases such as Crohn and ulcerative colitis (UC) are complexes diseases with unknown etiology. These illnesses result from intestinal microbiota, integrity and function of epithelial cells and immune system unbalance. UC is a chronic inflammatory disease with acute and intense inflammation manifestation. Immune response triggered by innate immunity cells and Toll like receptor (TLR) is essential for development and progress of UC. Many studies suggest an important role for short chain fatty acids in UC physiopathology evolution, especially butyrate. The last is physiologically produced by guts fibers bacterial fermentation and is referred to as possessing an anti-inflammatory effect in innate and adaptive immunity cells. In this way, studies on less toxics anti-inflammatory components for UC treatment constitute an important tool for intestinal inflammatory diseases healing. The goal of this work was to evaluate the effect of oral sodium butyrate administration in UC induced by dextran sodium sulfate (DSS) in wild mice C57BL/6 and TLR4 knockout (TLR4-/-). In the first stage of this work, using wild C57BL/6 mice, we demonstrated that oral treatment with sodium butyrate significantly improved colonic mucosal in mice that received DSS, as demonstrated by morphmetrics and clinical analyses as well as by myeloperoxidase (MPO) and eosinophil peroxydase (EPO) dosage. Furthermore, we also observed that oral treatment with butyrate reduced circulating monocytes frequency and preserved mesenteric lymph nodes CD4+ T cells as well as spleens myeloid dendritics cells (DCs) integrin expression density in similar levels of that found in control group. In the second stage, using TLR4-/-, we showed that oral treatment with butyrate was able to retain CD11b+ monocytes and CD11+bCD11c+ peripheral blood density expression in levels comparable with that seeing in control group. CD8+ T lymphocytes and macrophages CD11+bCD11c+ reduction effect in peripheral blood can also be observed demonstrating that oral administration of butyrate promotes phenotypic differentiation in innate adaptive immunity cells on different organs correlated to the immune system, even that TLR4-/- treatment was not so efficient as in wild type C57BL/6 mice. We conclude that through different actions, in intestinal mucosal protection as well as in innate immunity cells modulation, especially neutrophils and eosinophils, oral administration of butyrate represents a promising therapeutic agent for UC treatment, possibly by a signalization bias TLR4 dependent mechanism.