Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR–IκB Kinase–NF-κB Pathways in Dendritic Cells
| Autor: | Jung Mogg Kim, Hyun Ae Woo, Da Jeong Rho, Young Jeon Kim, Su Hyuk Ko, Nayoung Kim, Jong Ik Jeon |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
NF-E2-Related Factor 2 Immunology Gene Expression P70-S6 Kinase 1 IκB kinase Biology Microbiology Extracellular Vesicles Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Mice Knockout Host Response and Inflammation Helicobacter pylori TOR Serine-Threonine Kinases NF-κB Dendritic Cells Acquired immune system I-kappa B Kinase Cell biology Heme oxygenase 030104 developmental biology Infectious Diseases chemistry I-kappa B Proteins Parasitology Signal transduction Proto-Oncogene Proteins c-akt Heme Oxygenase-1 Signal Transduction 030215 immunology |
| Zdroj: | Infection and Immunity |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00190-16 |
| Popis: | Helicobacter pylori sheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses against H. pylori , and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. Although H. pylori -derived OMVs may contribute to the pathogenesis of H. pylori infection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role of H. pylori -derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crude H. pylori OMVs upregulated HO-1 expression. Crude OMVs obtained from a cagA -negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. Crude H. pylori OMVs activated signals of transcription factors such as NF-κB, AP-1, and Nrf2. Suppression of NF-κB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV-induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IκB kinase (IKK), NF-κB, and HO-1 expression in crude OMV-exposed DCs. These results suggest that H. pylori -derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR–IKK–NF-κB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses in H. pylori infection. |
| Databáze: | OpenAIRE |
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