Heme Oxygenase-1 Is a Critical Regulator of Nitric Oxide Production in Enterohemorrhagic Escherichia coli-Infected Human Enterocytes
| Autor: | Alain P. Gobert, Christine Martin, Thibaut de Sablet, Marjolaine Vareille, Anne-Lise Glasser, François Rannou, Natacha Thélier |
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| Rok vydání: | 2008 |
| Předmět: |
Small interfering RNA
Immunology Nitric Oxide Synthase Type II Protoporphyrins Biology Nitric Oxide medicine.disease_cause Nitric oxide Microbiology chemistry.chemical_compound Intestinal mucosa Cell Line Tumor Gene expression medicine Humans Immunology and Allergy RNA Small Interfering Heme Escherichia coli Escherichia coli Infections Innate immune system biochemical phenomena metabolism and nutrition Immunity Innate Heme oxygenase Enterocytes STAT1 Transcription Factor chemistry Enterohemorrhagic Escherichia coli bacteria Heme Oxygenase-1 |
| Zdroj: | The Journal of Immunology. 180:5720-5726 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.180.8.5720 |
| Popis: | Enterohemorrhagic Escherichia coli (EHEC) are the causative agent of hemolytic-uremic syndrome. In the first stage of the infection, EHEC interact with human enterocytes to modulate the innate immune response. Inducible NO synthase (iNOS)-derived NO is a critical mediator of the inflammatory response of the infected intestinal mucosa. We therefore aimed to analyze the role of EHEC on iNOS induction in human epithelial cell lines. In this regard, we show that EHEC down-regulate IFN-γ-induced iNOS mRNA expression and NO production in Hct-8, Caco-2, and T84 cells. This inhibitory effect occurs through the decrease of STAT-1 activation. In parallel, we demonstrate that EHEC stimulate the rapid inducible expression of the gene hmox-1 that encodes for the enzyme heme oxygenase-1 (HO-1). Knock-down of hmox-1 gene expression by small interfering RNA or the blockade of HO-1 activity by zinc protoporphyrin IX abrogated the EHEC-dependent inhibition of STAT-1 activation and iNOS mRNA expression in activated human enterocytes. These results highlight a new strategy elaborated by EHEC to control the host innate immune response. |
| Databáze: | OpenAIRE |
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