title: 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.
abstract: 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.
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors: Tetsuya
authors: T
authors: Tanigawa
authors: Toshio
authors: T
authors: Watanabe
authors: Kazuhide
authors: K
authors: Higuchi
authors: Hirohisa
authors: H
authors: Machida
authors: Hirotoshi
authors: H
authors: Okazaki
authors: Hirokazu
authors: H
authors: Yamagami
authors: Kenji
authors: K
authors: Watanabe
authors: Kazunari
authors: K
authors: Tominaga
authors: Yasuhiro
authors: Y
authors: Fujiwara
authors: Nobuhide
authors: N
authors: Oshitani
authors: Tetsuo
authors: T
authors: Arakawa