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Shiga Toxin Produced by Enterohemorrhagic Escherichia coli Inhibits PI3K/NF-κB Signaling Pathway in Globotriaosylceramide-3-Negative Human Intestinal Epithelial Cells
| Content Provider | Scilit |
|---|---|
| Author | Gobert, Alain P. Vareille, Marjolaine Glasser, Anne-Lise Hindré, Thomas de Sablet, Thibaut Martin, Christine |
| Copyright Year | 2007 |
| Description | Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli (EHEC) binds to endothelial cells expressing globotriaosylceramide-3 (Gb-3) and induces cell death by inhibiting translation. Nonetheless, the effects of Stx on human enterocytes, which lacks receptor Gb-3, remain less known. In this study, we questioned whether EHEC-derived Stx may modulate cellular signalization in the Gb-3-negative human epithelial cell line T84. Stx produced by EHEC was fixed and internalized by the cells. A weak activation of NF-κB was observed in T84 cells after EHEC infection. Cells infected with an isogenic mutant lacking stx1 and stx2, the genes encoding Stx, displayed an increased NF-κB DNA-binding activity. Consequently, the NF-κB-dependent CCL20 and IL-8 gene transcription and chemokine production were enhanced in T84 cells infected with the Stx mutant in comparison to the wild-type strain. Investigating the mechanism by which Stx modulates NF-κB activation, we showed that the PI3K/Akt signaling pathway was not induced by EHEC but was enhanced by the strain lacking Stx. Pharmacological inhibition of the PI3K/Akt signalization in EHEC ΔStx-infected T84 cells yielded to a complete decrease of NF-κB activation and CCL20 and IL-8 mRNA expression. This demonstrates that the induction of the PI3K/Akt/NF-κB pathway is potentially induced by EHEC, but is inhibited by Stx in Gb-3-negative epithelial cells. Thus, Stx is an unrecognized modulator of the innate immune response of human enterocytes. |
| Ending Page | 8174 |
| Page Count | 7 |
| Starting Page | 8168 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.178.12.8168 |
| Journal | The Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 178 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2007-06-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Death Innate Immune Nf Κb Signaling Pathway |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
