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Microbial Components Decrease Flagellin‐Induced IL‐8 Production through Toll Like Receptor (TLR) Signaling Pathway in Caco‐2 Cells
Author(s) -
Li Nan,
Quidgley Maria C,
Joseph Jessica,
Neu Josef
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.784.7
In the intestine, bacterial components activate innate responses that protect the host. The mechanism of this protection is poorly understood. We hypothesize that bacterial components, lipopolysaccharide (LPS), lipoteichoic acid (LTA) and low dose of flagellin (LDFL) reduce Interleukin‐8 (IL‐8) production in intestinal epithelial cells stimulated by the pathogenic ligand flagellin (FL) via the TLR signaling pathway. Caco‐2 cells were pretreated with various doses of LPS, LTA , or LDFL for 24 hours. Cells were then treated with FL 500 ng/mL for another 48 hours. IL‐8 production was measured in the cell culture medium by ELISA. Eighty four genes in the TLR signaling pathway were evaluated by RT Profiler PCR Array. FL at 500 ng/ml induced IL‐8 production by 19 fold (P<0.01). Pre‐treatment with LDFL at 20, 10 or 1 ng/ml reduced FL IL‐8 production by 61%, 52% and 40%, respectively (all p<0.05). LPS at 50 μg/ml decreased FL –induced IL‐8 production by 38% (p<0.05). LTA did not change FL‐induced IL‐8 production. FL up‐regulated CXCL10, IL1B, IL‐8, IRAK2, NFKB1 and IKB (all p < 0.05). Pre‐treatment with LDFL at 10 ng/ml down‐regulated FADD, FOS, MAP4K4, MyD88, TLR2, TLR3 and TNFERSF1A compared to FL(all p<0.05). LPS up‐regulated TLR6 compared to FL (p<0.05). These results demonstrate that LPS and LDFL provoke tolerance to FL‐induced IL‐8 production. These effects are mediated via multiple genes in TLR signaling pathway.