Regulation of microglial inflammatory response by sodium butyrate and short‐chain fatty acids

Abstract

1 Recent studies have shown that sodium butyrate and other short-chain fatty acids (SCFAs) can prevent inflammation in colon diseases. Our aim was to elucidate whether sodium butyrate and SCFAs regulate the inflammatory responses in different neural inflammation models in cell cultures. 2 Inflammatory responses to LPS-induced microglial activation were recorded by the secretion of nitric oxide (NO) and cytokines IL-6 and TNF-a and related to the changes in the DNA-binding activities of NF-kB complex. 3 We observed that sodium butyrate is strongly anti-inflammatory against LPS-induced responses in rat primary microglia as well as in hippocampal slice cultures and in neural cocultures of microglial cells, astrocytes and cerebellar granule neurons. 4 In murine N9 microglial cell line, instead, sodium butyrate and other SCFAs (propionate, valerate and caproate) enhanced the LPS-induced inflammatory response. 5 The pretreatment with butyrate before LPS exposure induced an equal or more enhanced response than simultaneous exposure with butyrate and LPS. This indicates that butyrate induces an adaptative response against microglial activation. 6 We also observed that butyrate treatment both in transformed N9 cells and in hippocampal slice cultures downregulates the NF-kB-binding capacity induced by LPS stimulation. 7 Our results show that butyrate is anti-inflammatory in primary, brain-derived microglial cells, as observed recently in colon diseases, but proinflammatory in transformed, proliferating N9 microglial cells, which may be related to the anticancer properties of butyrate observed in tumor cells.

Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

“…1C) and so it makes sense that it can serve as a control point for limiting the IR (Suuronen et al, 2003). Indeed, several studies have reported a decrease in the TLR4/NF-κB response to LPS following butyrate administration (Huuskonen et al, 2004;Wu et al, 2012). In addition to reductions in NF-κB family genes, we propose that butyrate limits the extent of the immune response to LPS by reducing the expression of additional genes shown to be effectors of the IR.…”

“…Here we report that butyrate supplementation increases plasma levels of LBP. However, this effect may be muted by the addition of butyrate, as several groups have reported reductions in the downstream effects of LPS-mediated induction of the immune system (Chakravortty et al, 2000;Huuskonen et al, 2004;Morikawa et al, 2004;Ni et al, 2010) under similar conditions. In addition, SAA, also an acute phase protein, was unaffected by the addition of butyrate.…”

“…Science Publications AJAVS addition, since butyrate has been shown to be beneficial in models of gastrointestinal disease in a variety of species (Segain et al, 2000;Huuskonen et al, 2004;Borthakur et al, 2008;Hamer et al, 2008;Thibault et al, 2010), we sought to also determine the efficacy of exogenous butyrate administration by studying changes in rumen epithelial gene expression. To this end, a microarray analysis, followed by qRT-PCR confirmation was completed based on information from existing databases to determine the importance of any affected metabolic pathways at the molecular level.…”

Epigenetic Regulation of Gene Expression in Physiological and Pathological Brain Processes

“…Cellularly, ischemic damage results in an increased transcription rate of genes that control cellular stress, inflammatory, and apoptotic response genes. Interestingly, several groups have reported that treatment with various HDACis, SAHA, SB, and TSA, both prior to and following stroke induction, confers neuroprotection (82,115,142,161,162,277,282,316). The idea that HDACis might be neuroprotective against ischemic cell damage originates in the observation that following cerebral artery occlusion, an animal model to induce ischemia, H3 acetylation levels show a pronounced decrease (82).…”

Epigenetics of Neural Repair Following Spinal Cord Injury

“…In mouse cells, sodium butyrate also inhibits hypoxia-induced iNOS protein and down-regulation of TNF-α messenger RNA, thus reducing the inflammatory response [143]. Sodium butyrate can also induce an adaptive response to LPS-stimulated microglial activation by attenuating NO, IL-6, and TNF secretion-all classic microglial inflammatory responses [144]. However, this anti-inflammatory activity may be specific to short-chain fatty acid HDACi, as the hydroxamate HDACi, TSA and SAHA, strongly potentiate the LPS-induced inflammatory response in primary microglial, neural co-cultures, and hippocampal slices [145].…”