# Short-Chain Fatty Acids Elicit Differential Expression of Growth Factors and Pro-Inflammatory Cytokines in Immortalized Rat Enteric Glial Cells

## TL;DR

Short-chain fatty acids like butyrate and propionate affect gene and protein expression in gut glial cells, influencing growth factors and inflammation.

## Contribution

The study reveals how SCFAs differentially modulate EGC expression of growth factors and cytokines.

## Key findings

- Butyrate increases IL-6 mRNA but not TGFβ-1 or GDNF significantly.
- High-dose SCFAs reduce TGFβ-1 and TNFα protein levels.
- Cytokine mRNA changes do not consistently reflect protein levels.

## Abstract

Background/Objectives: Enteric glial cells (EGCs) are non-neuronal cells of the enteric nervous system that contribute to intestinal homeostasis through interactions with the intestinal epithelium, enteric neurons, and resident intestinal immune cells. The objective of the current study was to determine how exposure of EGCs to short-chain fatty acids (SCFAs) would affect the expression of growth factors and pro-inflammatory cytokines, products of EGCs with known effects on intestinal epithelial barrier integrity. Methods: An enteroglial cell line was treated with low- (1 mM) or high- (10 mM) dose sodium butyrate or sodium propionate for 8 to 24 h, after which mRNA and protein levels of glial cell line-derived neurotrophic factor (GDNF), transforming growth factor β-1 (TGFβ-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured using quantitative polymerase chain reaction assays and Western immunoblotting. Results: Only butyrate treatment for 8 and 24 h was associated with modest changes in GDNF mRNA. Neither SCFA elicited changes in TGFβ-1 mRNA. Despite this, high-dose butyrate and propionate were associated with reduced basal levels of TGFβ-1 protein as early as 12 h after treatment. Only butyrate was associated with a significant reduction in basal TNFα expression, which was present up to 24 h post-treatment. However, both butyrate (low- and high-dose) and propionate (high-dose only) elicited marked increases in IL-6 expression at all time points examined. Changes in cytokine mRNA levels were not mirrored at the protein level. Conclusions: SCFAs directly influence growth factor and cytokine expression in EGCs, but the functional implications of these changes in expression within the complicated milieux of the intestinal environment remain to be explored.