Short-Chain Fatty Acids Suppress Lipopolysaccharide-Induced Production of Nitric Oxide and Proinflammatory Cytokines Through Inhibition of NF-κB Pathway in RAW264.7 Cells

Abstract

Short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber contribute a significant proportion of daily energy requirement. Furthermore, these compounds are modulators of macrophage function and potential targets for the development of new drugs. The aims of this study were to evaluate the effects of three types of SCFAs (sodium acetate (NaAc), sodium propionate (NaP), and sodium butyrate (NaB)) on the production of NO and inducible nitric oxide synthase (iNOS) and proinflammatory and antiinflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin (IL-1, IL-6, and IL-10)) and to observe the effect of NaAc on inhibiting lipopolysaccharide (LPS)-induced NF-κB activation in LPS-stimulated RAW264.7 cells. The results show that three types of SCFAs (acetate, propionate, and butyrate) reduced the production of proinflammatory factors, including TNF-α, IL-1β, IL-6, and NO, and inhibited the vitality of iNOS. Meanwhile, SCFAs enhanced the production of antiinflammatory cytokine IL-10 in lower concentrations (1-1,200 μmol/L). Like NaB, NaAC inhibited LPS-induced NF-κB activation. These results may hold promise on the role that SCFAs have on the prevention and treatment of various inflammatory conditions.

Short-chain fatty acids in control of body weight and insulin sensitivity

“…In vitro, acetate and butyrate can decrease lipopolysaccharide-stimulated release of tumour necrosis factor (TNF) from human neutrophils by ~33% and ~75%, respectively (P <0.01), 156 and inhibit lipopolysaccharide-induced nuclear factor κB (NF-κB) in lipopolysaccharide-stimulated murine macro phage cell lines. 157 In addition, in another in vitro study using human peripheral blood mononuclear cells, overnight incubation with acetate, propionate and butyrate in concentrations of 0.2-100 mmol/l inhibited lipopolysaccharide-induced production of TNF and IFN-γ. 158 Moreover, in vivo data showed that acute rectal and intravenous admini stration of sodium acetate (compared with saline) decreased plasma levels of TNF in women with obesity.…”

Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment

“…In 2012, Liu et al also demonstrated that butyrate, as well as, acetate and proprionate, decreased proinflammatory factor production and increased antiinflammatory cytokine release in a murine macrophage cell line. They showed that butyrate suppresses the production of TNF-α, pro-inflammatory interleukins (IL-1β and IL-6), and nitric oxide by inhibiting NF-κB pathway, while it also enhances anti-inflammatory IL-10 levels [45]. Ohira et al used a co-culture cell model to evaluate the effects of butyrate on the inflammatory responses promoted by the interaction of macrophages and adipocytes.…”

Protective Effects of Butyrate on Renal Ischemia-Reperfusion Injury in Rats

“…Since butyrate suppresses histone deacetylase, it was widely used as a therapeutic agent in patients with cancer [8][9][10][11]. A series of studies have reported that in addition to its anticancer activity, butyrate possesses potent anti-inflammatory and antiapoptotic effects, as well as markedly attenuates free radical formation [9,[12][13][14]. More recently, reports have demonstrated that butyrate may protect diverse organs against IRI [13][14][15][16].…”

“…Previous studies have reported the anticancer effects of butyrate [8,11]. More recently, butyrate has been investigated as a potential therapeutic agent for diseases associated with IRI because of its anti-Urol Int 2019;102:348-355 DOI: 10.1159/000497476 oxidant, anti-inflammatory, and antiapoptotic effects in vivo and in vitro [12][13][14]. Liu et al [15] reported that butyrate reduced hepatic IRI in rats by attenuating oxidative stress and apoptosis.…”