Lansoprazole, a Proton Pump Inhibitor, Suppresses Production of Tumor Necrosis Factor-alpha and Interleukin-1beta Induced by Lipopolysaccharide and Helicobacter Pylori Bacterial Components in Human Monocytic Cells via Inhibition of Activation of Nuclear Factor-kappaB and Extracellular Signal-Regulated Kinase.
Pathogenic bacterial components play critical roles in initiation of gastrointestinal inflammation via activation of intracellular signaling pathways which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Lansoprazole (LANSO), a proton pump inhibitor, has been widely used for the treatment of peptic ulcers and reflux esophagitis due to its potent acid-suppressive effect. It has also been reported to have anti-inflammatory effects. In this study we investigated the effects of LANSO on the production of TNF-alpha and IL-1beta induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 microM) significantly reduced mRNA expression and production of TNF-alpha and IL-1beta by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor kappaB-alpha (IkappaB-alpha) and phosphorylation of extracellular signal-regulated kinase (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO exerts anti-inflammatory effects by suppressing induction of TNF-alpha and IL-1beta via inhibition of nuclear factor (NF)-kappaB and ERK activation.
Tanigawa
Tetsuya
T
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Watanabe
Toshio
T
Higuchi
Kazuhide
K
Machida
Hirohisa
H
Okazaki
Hirotoshi
H
Yamagami
Hirokazu
H
Watanabe
Kenji
K
Tominaga
Kazunari
K
Fujiwara
Yasuhiro
Y
Oshitani
Nobuhide
N
Arakawa
Tetsuo
T