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)-α and interleukin (IL)-1β. 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-α and IL-1β induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 μM) significantly reduced mRNA expression and production of TNF-α and IL-1β by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor κB-α (IκB-α) 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-α and IL-1β via inhibition of nuclear factor (NF)-κB and ERK activation.

Several studies have reported a significant association between sleep disturbance and inflammatory bowel disease (IBD). The aim of the present study is to compare the clinical characteristics and the health-related quality of life (HR-QOL) of Japanese IBD patients with or without sleep disturbances, and to investigate the risk factors for disease flare in these patients. IBD patients were asked to complete a self-administered questionnaire including the Pittsburg sleep quality index and the 8-item short-form health survey. The information about disease flare within 1 year from enrollment in the study was analyzed with a multiple logistic regression model to identify risk factors for IBD flare-ups. The prevalence of sleep disturbances was 44.1 % (60 out of 136 IBD patients). Use of sleep medications was significantly higher in IBD patients with sleep disturbances whereas use of immuno modulators was significantly higher in IBD patients without sleep disturbances. The scores from all HR-QOL domains were significantly lower in patients with sleep disturbances than in patients without sleep disturbances. Fifty-one patients (37.5 %) had disease flare within 1 year from enrollment in the study and sleep disturbances were identified as a significant risk factor for disease flare (OR 3.09, 95 % CI 1.47–6.43). Our results indicate that sleep disturbances are common in Japanese IBD patients and are associated with poorer HR-QOL. Since the presence of sleep disturbances is a significant risk factor for IBD flare-ups, we encourage physicians to perform a careful examination of sleep disturbances in IBD patients.

Prostaglandin (PG) E₂ promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH), a catabolic enzyme for biological inactivation of PGE₂, in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15‐PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15‐PGDH expression to be an independent predictor of poor survival. The proportion of Ki67‐positive cells in 15‐PGDH‐negative adenocarcinoma was higher than that in 15‐PGDH‐positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase‐2 (COX‐2)‐positive tumors and those with COX‐2 negative tumors. In an in vitro study, use of specific siRNA to silence 15‐PGDH or a specific inhibitor of 15‐PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15‐PGDH. These findings suggest that reduction of 15‐PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma. (Cancer Sci 2009)