PMID- 17122965
OWN - NLM
STAT- MEDLINE
DCOM- 20070822
LR  - 20220410
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 55
IP  - 11
DP  - 2006 Nov
TI  - Molecular mechanisms involved in anti-inflammatory effects of proton pump 
      inhibitors.
PG  - 476-80
AB  - OBJECTIVE: Interleukin (IL)-8 has been reported to participate in neutrophil 
      infiltration in Helicobacter pylori (H. pylori)-induced gastritis in humans. In 
      this study, we investigated the anti-inflammatory actions beyond the suppression 
      of acid secretion by proton pump inhibitors (PPI), such as omeprazole and 
      lansoprazole, on IL-8 production by gastric epithelial cells (MKN45) and human 
      umbilical vein endothelial cells (HUVEC) and on the transendothelial migration of 
      polymorphonuclear neutrophils (PMN). MATERIALS AND METHODS: MKN45 and HUVEC were 
      stimulated with H. pylori water extract (HPE) and IL-1beta, respectively, and 
      nuclear factor kappa B (NFkappaB) activation and subsequent IL-8 production was 
      assessed in the absence or presence of PPI. We also assessed the effect of PPI on 
      IL-8-induced PMN transendothelial migration and on the alteration of cytoplasmic 
      calcium concentration in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated 
      PMN. RESULTS: HPE and IL-1beta induced a significant increase in IL-8 production 
      by MKN45 and HUVEC, respectively, along with NFkappaB activation, which was 
      significantly inhibited by PPI. PPI also inhibited the IL-8-induced 
      transendothelial migration of PMN and the fMLP-induced cytosolic calcium increase 
      in PMN. CONCLUSIONS: PPI attenuate PMN-dependent gastric mucosal inflammation 
      partly by interfering with NFkappaB activation in vascular endothelial cells and 
      gastric epithelial cells, and partly by modulating the calcium concentration of 
      PMN.
FAU - Handa, O
AU  - Handa O
AD  - Department of Biomedical Safety Science, Kyoto Prefectural University of 
      Medicine, 465 Kajii-cho, Kawaramachi-Hirokouji, Kamigyo-ku, Kyoto, Japan, 
      602-8566.
FAU - Yoshida, N
AU  - Yoshida N
FAU - Fujita, N
AU  - Fujita N
FAU - Tanaka, Y
AU  - Tanaka Y
FAU - Ueda, M
AU  - Ueda M
FAU - Takagi, T
AU  - Takagi T
FAU - Kokura, S
AU  - Kokura S
FAU - Naito, Y
AU  - Naito Y
FAU - Okanoue, T
AU  - Okanoue T
FAU - Yoshikawa, T
AU  - Yoshikawa T
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0K5C5T2QPG (Lansoprazole)
RN  - EC 6.- (Ligases)
RN  - EC 6.- (guanosine 3',5'-polyphosphate synthetases)
RN  - KG60484QX9 (Omeprazole)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/pharmacology
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/drug effects/metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Epithelium/metabolism/pathology
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - Lansoprazole
MH  - Ligases/metabolism
MH  - NF-kappa B/metabolism
MH  - Neutrophils/cytology/drug effects
MH  - Omeprazole/pharmacology
MH  - *Proton Pump Inhibitors
MH  - Stomach Neoplasms/metabolism/pathology
EDAT- 2006/11/24 09:00
MHDA- 2007/08/23 09:00
CRDT- 2006/11/24 09:00
PHST- 2006/11/24 09:00 [pubmed]
PHST- 2007/08/23 09:00 [medline]
PHST- 2006/11/24 09:00 [entrez]
AID - 10.1007/s00011-006-6056-4 [doi]
PST - ppublish
SO  - Inflamm Res. 2006 Nov;55(11):476-80. doi: 10.1007/s00011-006-6056-4.