Role of Muc1 in Helicobacter pylori gastric mucosal inflammation (90.15)

Abstract Helicobacter pylori (Hp) is a human pathogen that inhabits the stomach and duodenum. Hp causes chronic inflammation of the gastric mucosa (gastritis) that is strongly linked with the sequential progression to atrophy, metaplasia, dysplasia, and stomach cancer. However, greater than 80% of individuals infected with Hp are asymptomatic and it is unknown what factors influence the incidence and character of Hp-associated gastric disorders. Our previous studies demonstrated that the Muc1 epithelial mucin glycoprotein counter-regulates bacterial inflammation. Therefore, we investigated the role of Muc1 in controlling inflammatory responses to Hp infection. Muc1 knockout mice exhibited increased bacterial colonization of the stomach and greater inflammatory cytokine/chemokine responses compared with wild type mice following experimental Hp infection. Overexpression of Muc1 in human gastric AGS cells was correlated with decreased NF-κB activation and IL-8 production compared with cells expressing normal levels of Muc1. Conversely, knockdown of Muc1 expression in AGS cells was associated with greater activation of ERK1/2, increased phosphorylation of IκBα, augmented activation and nuclear translocation of NF-κB, and enhanced production of IL-8. Based on these results, we conclude that Muc1 plays an anti-inflammatory role in Hp gastric infection and that decreased Muc1 expression in a subset of Hp-infected individuals promotes the development of chronic gastritis and adenocarcinoma.