PMID- 21789261
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 7
DP  - 2011
TI  - Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori 
      protein (HP986) points to its role in chronic persistence.
PG  - e22530
LID - 10.1371/journal.pone.0022530 [doi]
LID - e22530
AB  - Helicobacter pylori induces cytokine mediated changes in gastroduodenal 
      pathophysiology, wherein, the activated macrophages at the sub-mucosal space play 
      a central role in mounting innate immune response against the antigens. The 
      bacterium gains niche through persistent inflammation and local 
      immune-suppression causing peptic ulcer disease or chronic gastritis; the latter 
      being a significant risk factor for the development of gastric adenocarcinoma. 
      What favors persistence of H. pylori in the gastric niches is not clearly 
      understood. We report detailed characterization of a functionally unknown gene 
      (HP986), which was detected in patient isolates associated with peptic ulcer and 
      gastric carcinoma. Expression and purification of recombinant HP986 (rHP986) 
      revealed a novel,  approximately 29 kDa protein in biologically active form which associates 
      with significant levels of humoral immune responses in diseased individuals 
      (p<0.001). Also, it induced significant levels of TNF-alpha and Interleukin-8 in 
      cultured human macrophages concurrent to the translocation of nuclear 
      transcription factor-kappaB (NF-kappaB). Further, the rHP986 induced apoptosis of 
      cultured macrophages through a Fas mediated pathway. Dissection of the underlying 
      signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to 
      lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 
      through computational and experimental approaches. Independent proinflammatory 
      and apoptotic responses triggered by rHP986 as shown in this study point to its 
      role, possibly as a survival strategy to gain niche through inflammation and to 
      counter the activated macrophages to avoid clearance.
FAU - Alvi, Ayesha
AU  - Alvi A
AD  - Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, 
      Hyderabad, India.
FAU - Ansari, Suhail A
AU  - Ansari SA
FAU - Ehtesham, Nasreen Z
AU  - Ehtesham NZ
FAU - Rizwan, Mohammed
AU  - Rizwan M
FAU - Devi, Savita
AU  - Devi S
FAU - Sechi, Leonardo A
AU  - Sechi LA
FAU - Qureshi, Insaf A
AU  - Qureshi IA
FAU - Hasnain, Seyed E
AU  - Hasnain SE
FAU - Ahmed, Niyaz
AU  - Ahmed N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110715
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bacterial Proteins)
RN  - 0 (FAS protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Apoptosis
MH  - Bacterial Proteins/chemistry/*metabolism
MH  - Gastrointestinal Diseases/metabolism/microbiology/pathology
MH  - Genetic Loci/genetics
MH  - Helicobacter Infections/*metabolism/microbiology/pathology
MH  - Helicobacter pylori/isolation & purification/*metabolism
MH  - Humans
MH  - Immunity, Humoral
MH  - Inflammation Mediators/*metabolism
MH  - Interleukin-8/metabolism
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - Sequence Alignment
MH  - Sequence Analysis, Protein
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - fas Receptor/metabolism
PMC - PMC3137634
COIS- Competing Interests: Niyaz Ahmed is a Section Editor of PLoS ONE and a member of 
      the PLoS International Advisory Group; this however does not alter the authors' 
      adherence to PLoS policies and principles on a whole.
EDAT- 2011/07/27 06:00
MHDA- 2011/12/13 00:00
PMCR- 2011/07/15
CRDT- 2011/07/27 06:00
PHST- 2011/06/10 00:00 [received]
PHST- 2011/06/23 00:00 [accepted]
PHST- 2011/07/27 06:00 [entrez]
PHST- 2011/07/27 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2011/07/15 00:00 [pmc-release]
AID - PONE-D-11-10342 [pii]
AID - 10.1371/journal.pone.0022530 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(7):e22530. doi: 10.1371/journal.pone.0022530. Epub 2011 Jul 15.