Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-alpha-induced interleukin-8 production in Caco-2 cells.
Certain probiotic bacteria show anti-inflammatory activity after being heat killed, whereas others do not, suggesting that the gastrointestinal environment may alter the activity of probiotic bacteria. Occasionally, probiotics are provided when a patient is also being treated with oral antibiotics; this may have an effect on the probiotic activity. We hypothesized that Lactobacillus rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-alpha (TNFalpha)-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor kappaB (NFkappaB)/inhibitor of kappaB (IkappaB) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 10(4) to 10(10) cfu/L, in the presence or absence of antibiotics and TNFalpha in the media. TNFalpha-induced production of IL-8 by Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses of live LGG without TNFalpha in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNFalpha-induced IL-8 production (P < 0.01), but by itself did not increase IL-8 production at higher doses as markedly as live LGG (P < 0.05). LGG reduced the TNFalpha-induced NFkappaB translocation to the nucleus and lessened the decrease in IkappaB in the cytoplasm (P < 0.05). LGG reduced TNFalpha-induced IL-8 production by affecting the NFkappaB/IkappaB pathway in Caco-2 cells. High doses of live LGG markedly increased IL-8 production, but heat-killed LGG caused only a slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate inflammation with a lower potential than live LGG at high doses to cause inflammation.
Zhang
Liyan
L
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610-0296, USA.
Li
Nan
N
Caicedo
Ricardo
R
Neu
Josef
J
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D007778:Lactobacillus; D016133:Polymerase Chain Reaction; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha