As a participant in the mucosal immune response, the intestinal epithelial cell must respond to a variety of stimuli, including lactic acid bacteria (LAB) consumed in the diet. The objective of this study was to compare the abilities of several strains of LAB to modulate cytokine secretion by human intestinal epithelial cell (IEC) line HT-29. Certain strains of Lactobacillus rhamnosus, Lactobacillus delbrueckii, and Lactobacillus acidophilus suppressed the production of the chemokine RANTES by stimulated HT-29 IEC, although the magnitude of this suppression varied depending on the nature of the bacterial growth medium. Similarly, specific strains showed growth condition-dependent suppression of HT-29 interleukin-8 (IL-8) production. Strain-dependent effects were also seen for the suppression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) production. The binding of several of these bacterial strains to the HT-29 cell line was also examined. Different strains were found to have differing abilities to interact with IEC, with L. rhamnosus R0011 being the strain that generally had the most extensive effects on HT-29 cytokine production and also bound to HT-29 IEC most effectively. Modulation of IEC cytokine production has the potential to profoundly affect the mucosal microenvironment, influencing the immune response to pathogens and other ingested antigens.

We have identified three novel, rarely expressed human genes that encode new members of the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene family based on sequence homology. BPI and other members of the LT/LBP family are structurally related proteins capable of binding phospholipids and lipopolysaccharides. Real-time PCR studies indicate that BPIL1 and BPIL3 are highly expressed in hypertrophic tonsils. In situ hybridization analysis of BPIL2 shows prominent expression in skin specimens from psoriasis patients. BPIL1 and BPIL3 map to Chromosome 20q11; thus, these novel genes form a cluster with BPI and two other members of the LT/LBP gene family on the long arm of human Chr 20. BPIL2maps to Chr 22q13. The exon/intron organization of all three genes is highly conserved with that of BPI, suggesting evolution from a common ancestor.

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.

OHNSON OHNSON potential of fermented food components through interactions with intestinal epithelial cells.

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