Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates DSS-induced colitis
| Autor: | Luther, Jay, Owyang, Stephanie Y., Takeuchi, Tomomi, Cole, Tyler, Zhang, Min, Liu, Maochang, Erb-Downward, John, Rubenstein, Joel H., Kao, John Y. |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
DNA
Bacterial Male Helicobacter pylori Dextran Sulfate Down-Regulation Dendritic Cells Middle Aged Colitis Inflammatory Bowel Diseases Interleukin-12 Article Mice Inbred C57BL Mice Chronic Disease Interferon Type I Escherichia coli Animals Cytokines Humans Female Intestinal Mucosa Immunity Mucosal Aged |
| Popis: | Epidemiological data have recently emerged to suggest Helicobacter pylori may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between H pylori and IBD has not been described.The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow-derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (DC) was analysed by cytokine production. The effect of H pylori DNA on Escherichia coli DNA production of type I IFN and IL-12 was assessed. The in-vivo significance of H pylori DNA suppression was assessed in a dextran sodium sulphate (DSS) model of colitis. The systemic levels of type I IFN were assessed in H pylori-colonised and non-colonised patients.H pylori DNA has a significantly elevated IRS:ISS ratio. In-vitro experiments revealed the inability of H pylori DNA to stimulate type I IFN or IL-12 production from mouse BMDC or human plasmacytoid DC. H pylori DNA was also able to suppress E coli DNA production of type I IFN and IL-12. The administration of H pylori DNA before the induction of DSS colitis significantly ameliorated the severity of colitis compared with E coli DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in H pylori-colonised patients than non-colonised controls.This study indicates that H pylori DNA has the ability to downregulate pro-inflammatory responses from DC and this may partly explain the inverse association between H pylori and IBD. |
| Databáze: | OpenAIRE |
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