Butyric acid inhibits a Toll-like receptor 2 agonist-mediated increase of Toll-like receptor 3-induced chemokine production by HT-29 intestinal epithelial cells (IRC10P.413)

Abstract

Abstract The intestinal epithelium interacts with varied microbial components and metabolites, integrating multiple signals that influence immunity. We examined the time and dose-dependent effects of a Toll-Like Receptor (TLR) 2 agonist lipoprotein Pam3Cys (P3C) and the bacterial fermentation metabolite butyric acid (BA) (10mM and 25mM) on TLR3 agonist (poly(I:C)) (pIC)-induced chemokine production by HT-29 intestinal epithelial cells (IEC). Pre-treatment of HT-29 IEC with P3C enhanced (p(IC))-induced IL-8 production. However, pre-treatment of HT-29 IEC with P3C and 25mM BA together inhibited p(I:C)-induced IL-8 production, suggesting BA blocked the enhancing effect of this TLR2 agonist on TLR3-induced chemokine production. This inhibitory effect was not observed when IEC were pre-treated with a lower concentration of BA (10mM). Co-incubation of IEC with P3C and p(I:C) did not enhance TLR3 agonist-induced IL-8 production, while co-incubation with 10mM or 25mM BA acid significantly reduced p(I:C)-induced IL-8 and CXCL-10 production by HT-29 IEC. In addition, a p38 blocker (SB203580) significantly inhibited p(I:C)-induced IL-8 production by HT-29 IEC, while co-incubation with SB203580 and 10mM BA showed no additive inhibition. These findings suggest that while TLR2 agonists can upregulate TLR3-induced chemokine production, butyric acid inhibits this process, and the effects of TLR2 agonists and BA are dependent on timing of contact with IEC relative to TLR3 agonist stimulation.