PMID- 27185786
OWN - NLM
STAT- MEDLINE
DCOM- 20170516
LR  - 20211204
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 84
IP  - 8
DP  - 2016 Aug
TI  - Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce 
      Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR-IkappaB 
      Kinase-NF-kappaB Pathways in Dendritic Cells.
PG  - 2162-2174
LID - 10.1128/IAI.00190-16 [doi]
AB  - 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-kappaB, AP-1, and 
      Nrf2. Suppression of NF-kappaB 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 IkappaB kinase (IKK), NF-kappaB, 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-kappaB 
      signaling. Following this induction, increased HO-1 expression in DCs may 
      modulate inflammatory responses in H. pylori infection.
CI  - Copyright (c) 2016 Ko et al.
FAU - Ko, Su Hyuk
AU  - Ko SH
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul, South Korea.
FAU - Rho, Da Jeong
AU  - Rho DJ
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul, South Korea.
FAU - Jeon, Jong Ik
AU  - Jeon JI
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul, South Korea.
FAU - Kim, Young-Jeon
AU  - Kim YJ
AD  - Department of Biotechnology, Joongbu University, Gumsan, South Korea.
FAU - Woo, Hyun Ae
AU  - Woo HA
AD  - Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South 
      Korea.
FAU - Kim, Nayoung
AU  - Kim N
AD  - Department of Internal Medicine, Seoul National University Bundang Hospital, 
      Seongnam, South Korea.
FAU - Kim, Jung Mogg
AU  - Kim JM
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul, South Korea jungmogg@hanyang.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20160721
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/*metabolism
MH  - Extracellular Vesicles/*metabolism
MH  - Gene Expression
MH  - Helicobacter pylori/*metabolism
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - I-kappa B Proteins/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4962631
EDAT- 2016/05/18 06:00
MHDA- 2017/05/17 06:00
PMCR- 2016/07/21
CRDT- 2016/05/18 06:00
PHST- 2016/05/03 00:00 [received]
PHST- 2016/05/06 00:00 [accepted]
PHST- 2016/05/18 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/05/17 06:00 [medline]
PHST- 2016/07/21 00:00 [pmc-release]
AID - IAI.00190-16 [pii]
AID - 00190-16 [pii]
AID - 10.1128/IAI.00190-16 [doi]
PST - epublish
SO  - Infect Immun. 2016 Jul 21;84(8):2162-2174. doi: 10.1128/IAI.00190-16. Print 2016 
      Aug.