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© 2005 The American Society for Nutritional Sciences J. Nutr. 135:1752-1756, July 2005


Nutritional Immunology

Alive and Dead Lactobacillus rhamnosus GG Decrease Tumor Necrosis Factor-{alpha}–Induced Interleukin-8 Production in Caco-2 Cells

Liyan Zhang1,*, Nan Li, Ricardo Caicedo and Josef Neu2

Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610-0296 and * Fujian Provincial Maternity and Child Health Hospital, Neonatology, Fuzhou, Fujian, China 350001

2To whom correspondence should be addressed. E-mail: neuj{at}peds.ufl.edu.

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} (TNF{alpha})-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor {kappa}B (NF{kappa}B)/inhibitor of {kappa}B (I{kappa}B) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 104 to 1010 cfu/L, in the presence or absence of antibiotics and TNF{alpha} in the media. TNF{alpha}-induced production of IL-8 by Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses of live LGG without TNF{alpha} in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNF{alpha}-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 TNF{alpha}-induced NF{kappa}B translocation to the nucleus and lessened the decrease in I{kappa}B in the cytoplasm (P < 0.05). LGG reduced TNF{alpha}-induced IL-8 production by affecting the NF{kappa}B/I{kappa}B 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.


KEY WORDS: • probiotic bacteria • intestinal epithelial cells • interleukin-8 • nuclear factor {kappa}B/inhibitor of {kappa}B




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