Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Linesin vitro

Abstract

Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs.

Regulation of immune cell function by short‐chain fatty acids

“…Iraporda et al 29 found that SCFAs (mainly, butyrate and propionate) reduce the expression of CXCL8 and CCL20 by Caco‐2 cells in vitro in response to flagellin stimulation, an effect that was not related to GPCRs activation. The inhibitory effect of the SCFAs on CXCL8, an important neutrophil chemoattractant, was also observed in other IECs cell lines and was associated with the inhibition of HDAC activity 30 …”

“…SCFAs interact with neutrophils and modulate their recruitment, effector function and survival at different tissues (reviewed in Rodrigues et al 33 ). These bacterial metabolites alter neutrophils recruitment by their ability to regulate the production of inflammatory mediators including cytokines that activate endothelial cells such as TNF‐α and IL‐17 and neutrophil‐chemoattractants such as CXCL1 and CXCL8 by different cells 26 , 28 , 29 , 30 , 34 , 35 . In addition, SCFAs activation of FFAR2 in neutrophils has been shown to induce their chemotaxis 7 , 36 , 37 …”

“…The inhibitory effect of the SCFAs on CXCL8, an important neutrophil chemoattractant, was also observed in other IECs cell lines and was associated with the inhibition of HDAC activity. 30 SCFAs also act on the epithelial barrier function itself. In this context, these bacterial metabolites not only increase the production of IL-18, a cytokine that contributes to the intestinal epithelium homeostasis, but also act by other mechanisms including stabilization of the HIF.…”

“…These bacterial metabolites alter neutrophils recruitment by their ability to regulate the production of inflammatory mediators including cytokines that activate endothelial cells such as TNF-α and IL-17 and neutrophil-chemoattractants such as CXCL1 and CXCL8 by different cells. 26,[28][29][30]34,35 In addition, SCFAs activation of FFAR2 in neutrophils has been shown to induce their chemotaxis. 7,36,37 Studies using human and rodent neutrophils (in this latter case, elicited cells) have found that SCFAs modify their production of inflammatory cytokines.…”

Prebiotics and Probiotics in Allergy: Potential Mechanisms of Prebiotics’ and Probiotics’ Actions in Allergy - (Part 1)

“…Butyrate may also modify epithelial cell gene expression, for example IL-8 and monocyte chemoattractant protein 1, and this in turn would change the signaling of the epithelial cell to the mucosal immune system [15,16]. SCFA cause an altered lymphocyte numbers in the spleen and intestinal mucosa in addition to cytokine formation [17].…”