PMID- 14631383
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20091119
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 84
IP  - 1
DP  - 2004 Jan
TI  - Helicobacter pylori in a Korean isolate activates mitogen-activated protein 
      kinases, AP-1, and NF-kappaB and induces chemokine expression in gastric 
      epithelial AGS cells.
PG  - 49-62
AB  - Oxidant-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB), and 
      activator protein-1 (AP-1) have been considered as the regulators of inducible 
      genes such as chemokines. Since oxygen radicals are considered as an important 
      regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric 
      ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and 
      monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-kappaB and/or 
      AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and 
      MAPK cascade regulate AP-1 activation. The present study aims to investigate 
      whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines 
      (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-kappaB in gastric 
      epithelial AGS cells, and whether these transcriptional regulations of chemokines 
      are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun 
      (TAM-67), and IkappaBalpha (MAD-3) or treatment with MAPK inhibitors (U0126 for 
      extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, 
      virulence factors of HP99 were characterized by PCR analysis for the isolated 
      DNA. As a result, HP99 is identified as cagA+, vacA s1b, m2, iceA1 H. pylori 
      strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and 
      MCP-1 via mediation of MAPK, AP-1, and NF-kappaB. Transfection with mutant genes 
      for Ras, c-Jun, and IkappaBalpha and treatment with MAPK inhibitors suppressed H. 
      pylori-induced activation of transcription factors (NF-kappaB, AP-1) and 
      expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK 
      cascade may act as the upstream signaling for the activation of AP-1 and 
      NF-kappaB, which induce chemokine expression in H. pylori-infected AGS cells. 
      Specific targeting of the activation of NF-kappaB and AP-1 may be effective for 
      the prevention or treatment of gastric inflammation associated with H. pylori 
      infection.
FAU - Seo, Ji Hye
AU  - Seo JH
AD  - Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 
      Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 
      Korea.
FAU - Lim, Joo Weon
AU  - Lim JW
FAU - Kim, Hyeyoung
AU  - Kim H
FAU - Kim, Kyung Hwan
AU  - Kim KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA, Bacterial)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Virulence Factors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/genetics/*metabolism
MH  - DNA, Bacterial/analysis/genetics
MH  - Gastric Mucosa/metabolism/pathology
MH  - Gene Expression Regulation, Bacterial
MH  - Helicobacter Infections/pathology/physiopathology
MH  - Helicobacter pylori/pathogenicity/*physiology
MH  - Humans
MH  - Interleukin-8/genetics/*metabolism
MH  - Mitogen-Activated Protein Kinases/*biosynthesis
MH  - NF-kappa B/*biosynthesis
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Transcription Factor AP-1/*biosynthesis
MH  - Virulence Factors/genetics
EDAT- 2003/11/25 05:00
MHDA- 2004/02/18 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
AID - 3700010 [pii]
AID - 10.1038/sj.labinvest.3700010 [doi]
PST - ppublish
SO  - Lab Invest. 2004 Jan;84(1):49-62. doi: 10.1038/sj.labinvest.3700010.