Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-kappaB activation.

Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells (IECs) in in vitro models both of the non-inflamed and inflamed intestinal epithelium. A reporter gene system in HT-29 cells was used to measure levels of NF-kappaB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. None of the bifidobacteria tested induced activation of nuclear factor kappaB (NF-kappaB) indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- (LPS-) induced NF-kappaB activation in a dose- and strain-dependent manner. In contrast, NF-kappaB activation in response to challenge with tumor necrosis factor-alpha (TNF-alpha) was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibition-positive bifidobacteria, LPS-induced inhibition of NF-kappaB activation was accompanied by a dose-dependent decrease of interleukin 8 (IL-8) secretion and by lower mRNA levels for IL-8, TNF-alpha, cyclooxygenase 2 (Cox-2), and intercellular adhesion molecule 1 (ICAM-1). Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.