Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 58, Issue 10, Pages 2080-2093Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201400218
Keywords
Anti-inflammatory activity; Extracellular polysaccharides; L. delbrueckii; PIE cells; TLR2; TLR4; TLR negative regulators
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Funding
- Japan Society for the Promotion of Science (JSPS) [21380164, 24380146, 23658216]
- JSPS (Postdoctoral Fellowship for Foreign Researchers) [25-03397]
- Grants-in-Aid for Scientific Research [23658216, 13F03397] Funding Source: KAKEN
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Scope: Immunobiotics are known tomodulate intestinal immune responses by regulating Toll-like receptor (TLR) signaling pathways, which are responsible for the induction of cytokines and chemokines in response to microbial-associated molecular patterns. However, little is known about the immunomodulatory activity of compounds or molecules from immunobiotics. Methods and results: We evaluated whether Lactobacillus delbrueckii subsp. delbrueckii TUA4408L (Ld) or its extracellular polysaccharide (EPS): acidic EPS (APS) and neutral EPS (NPS), modulated the response of porcine intestinal epitheliocyte (PIE) cells against Entero-toxigenic Escherichia coli (ETEC) 987P. The roles of TLR2, TLR4, and TLR negative regulators in the immunoregulatory effects were also studied. ETEC-induced inflammatory cytokines were downregulated when PIE cells were prestimulated with both Ld or EPSs. Ld, APS, and NPS inhibited ETEC mediated mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappa B) activation by upregulating TLR negative regulators. The capability of Ld to suppress inflammatory cytokines was diminished when PIE cells were blocked with anti-TLR2 antibody, while APS failed to suppress inflammatory cytokines when cells were treated with anti-TLR4 antibody. Induction of Ca2+ fluxes in TLR knockdown cells confirmed that TLR2 plays a principal role in the immunomodulatory action of Ld, while the activity of APS is mediated by TLR4. In addition, NPS activity depends on both TLR4 and TLR2. Conclusion: Ld and its EPS have the potential to be used for the development of anti-inflammatory functional foods to prevent intestinal diseases in both humans and animals.
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