PMID- 24223737
OWN - NLM
STAT- MEDLINE
DCOM- 20140820
LR  - 20240319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Helicobacter pylori protein JHP0290 binds to multiple cell types and induces 
      macrophage apoptosis via tumor necrosis factor (TNF)-dependent and independent 
      pathways.
PG  - e77872
LID - 10.1371/journal.pone.0077872 [doi]
LID - e77872
AB  - Activated macrophages at the sub-mucosal space play a major role in generating 
      innate immune responses during H. pylori infection. Final disease outcome largely 
      depends on how H. pylori and bacterium-derived products modulate macrophage 
      responses. Here, we report that JHP0290, a functionally unknown protein from H. 
      pylori, regulates macrophage functions. Recombinant purified JHP0290 (rJHP0290) 
      had the ability to bind to several cell types including macrophages, human 
      gastric epithelial cell lines, human monocyte-derived dendritic cells (MoDC) and 
      human neutrophils. Exposure to rJHP0290 induced apoptosis in macrophages 
      concurrent with release of proinflammatory cytokine tumor necrosis factor (TNF). 
      A mutant strain of H. pylori disrupted in the jhp0290 gene was significantly 
      impaired in its ability to induce apoptosis and TNF in macrophages confirming the 
      role of endogenous protein in regulating macrophage responses. Intracellular 
      signaling involving Src family of tyrosine kinases (SFKs) and ERK MAPK were 
      required for rJHP0290-induced TNF release and apoptosis in macrophages. 
      Furthermore, rJHP0290-induced TNF release was partly dependent on activation of 
      nuclear transcription factor-kappaB (NF-kappaB). Neutralizing antibodies against TNF 
      partially blocked rJHP0290-induced macrophage apoptosis indicating 
      TNF-independent pathways were also involved. These results provide mechanistic 
      insight into the potential role of the protein JHP0290 during H. 
      pylori-associated disease development. By virtue of its ability to induce TNF, an 
      acid suppressive proinflammatory cytokine and induction of macrophage apoptosis, 
      JHP0290 possibly helps in persistent survival of the bacterium inside the 
      stomach.
FAU - Pathak, Sushil Kumar
AU  - Pathak SK
AD  - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm 
      University, Stockholm, Sweden.
FAU - Tavares, Raquel
AU  - Tavares R
FAU - de Klerk, Nele
AU  - de Klerk N
FAU - Spetz, Anna-Lena
AU  - Spetz AL
FAU - Jonsson, Ann-Beth
AU  - Jonsson AB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131101
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bacterial Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Bacterial Proteins/immunology/*metabolism
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Helicobacter pylori/*immunology/metabolism
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System
MH  - Macrophages/*physiology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - Transcription Factor AP-1/metabolism
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*physiology
PMC - PMC3815203
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/14 06:00
MHDA- 2014/08/21 06:00
PMCR- 2013/11/01
CRDT- 2013/11/14 06:00
PHST- 2013/07/19 00:00 [received]
PHST- 2013/09/09 00:00 [accepted]
PHST- 2013/11/14 06:00 [entrez]
PHST- 2013/11/14 06:00 [pubmed]
PHST- 2014/08/21 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - PONE-D-13-29860 [pii]
AID - 10.1371/journal.pone.0077872 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 1;8(11):e77872. doi: 10.1371/journal.pone.0077872. eCollection 
      2013.