Article

Butyrate induces apoptosis in murine macrophages via caspase-3, but independent of autocrine synthesis of tumor necrosis factor and nitric oxide

Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Brazilian Journal of Medical and Biological Research (Impact Factor: 1.01). 03/2002; 35(2):161-73. DOI: 10.1590/S0100-879X2002000200004
Source: PubMed

ABSTRACT

We demonstrated that 4 mM butyrate induces apoptosis in murine peritoneal macrophages in a dose- and time-dependent manner as indicated by studies of cell viability, flow cytometric analysis of annexin-V binding, DNA ladder pattern and the determination of hypodiploid DNA content. The activity of caspase-3 was enhanced during macrophage apoptosis induced by butyrate and the caspase inhibitor z-VAD-FMK (100 microM) inhibited the butyrate effect, indicating the major role of the caspase cascade in the process. The levels of butyrate-induced apoptosis in macrophages were enhanced by co-treatment with 1 microg/ml bacterial lipopolysaccharide (LPS). However, our data indicate that apoptosis induced by butyrate and LPS involves different mechanisms. Thus, LPS-induced apoptosis was only observed when macrophages were primed with IFN-gamma and was partially dependent on iNOS, TNFR1 and IRF-1 functions as determined in experiments employing macrophages from various knockout mice. In contrast, butyrate-induced macrophage apoptosis was highly independent of IFN-gamma priming and of iNOS, TNFR1 and IRF-1 functions.

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Available from: Jacqueline I Alvarez-Leite, Jun 22, 2015
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    • "The mechanism by which butyrate induces cell death in different cell types are not known, but there is evidence that butyrate triggers the activation of the caspase cascade in cancer cells leading to their death by apoptosis (Medina et al., 1997; Ramos et al., 2002; Ruemmele et al., 1999). Other authors have also demonstrated that high butyrate concentrations induce caspase-3 activation in peritoneal macrophages (Ramos et al., 2002) or in peripheral blood mononuclear cells (Kurita-Ochiai et al., 1999). To our knowledge, this is the first manuscript which describes a link between apoptosis and cytokine modulation by butyrate. "
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