Interactions in the mucosal microenvironment: vasoactive intestinal peptide modulates the down-regulatory action of Lactobacillus rhamnosus on LPS-induced interleukin-8 production by intestinal epithelial cells

Intestinal epithelial cells (IECs) act as a key point of initial contact with bacteria in the microenvironment of the intestinal tract. Interactions between IECs and bacteria lead to alterations in IEC activity, including modified cytokine secretion patterns, which may influence the mucosal immune response. IECs respond to lipopolysaccharide (LPS) from gramnegative bacteria by production of pro-inflammatory cytokines, including interleukin-8 (IL-8). Two strains of Lactobacillus rhamnosus , R0011 and R0049, were able to down-regulate LPS-induced IL-8 production by the human IEC line HT-29. Similar results were seen with KATO III gastric epithelial cells, suggesting a possible route for anti-inflammatory actions by L. rhamnosus . To further explore potential interactions in the gastrointestinal mucosal microenvironment, the effects of the neuropeptide vasoactive intestinal peptide (VIP) on the actions of L. rhamnosus R0011 were examined. VIP blocked the ability of this strain to down-regulate both constitutive and LPS-induced IL-8 production, suggesting that interactions between lactic acid bacteria (LAB) and IECs can be influenced by neuropeptides released into intestinal tissues. High levels of protein kinase A (PKA) and protein kinase C (PKC) activation rendered IEC refractory to the down-regulatory effects of L. rhamnosus on IL-8 production. L. rhamnosus R0011 induces moderate elevation of intracellular cAMP levels, indicating that its actions may, at least in part, be mediated through this signalling pathway in IECs. Key words: interleukin-8, vasoactive intestinal peptide, lactobacilli, probiotics, intestinal epithelial cell