The Helicobacter pylori type IV secretion system promotes IL-8 synthesis in a model of pediatric airway epithelium via p38 MAP kinase

Abstract

Epidemiologic studies have reported an inverse relationship between childhood Helicobacter pylori infection and development of allergic asthma. Because lung epithelium plays an important role in allergic asthma pathogenesis, we hypothesized that H. pylori may directly influence airway epithelial cell innate immune function, particularly in early childhood. To test our hypothesis, we established an in vitro H. pylori infection model using primary tracheobronchial epithelial cell cultures derived from infant, juvenile and adult rhesus monkeys. Airway epithelial cell cultures were infected with wild-type or cag pathogenicity island mutant H. pylori strains, followed by evaluation of IL-8 and IL-6 protein synthesis. We found that H. pylori primarily increased IL-8 synthesis in a MOI and age-dependent fashion, with a greater than 4-fold induction in infant versus adult cultures. H. pylori-induced IL-8 synthesis in infant and juvenile cultures was significantly reduced by cag pathogenicity island mutants, indicating a requirement for the type IV secretion system. Although peptidoglycan recognition of nucleotide binding oligomerization domain-containing protein 1 (NOD1) and NF-kappaB have been implicated as key cytokine signaling molecules for H. pylori infection in gastric epithelium, NOD1 (ML130) or NF-kappaB (JSH-23) inhibitors minimally affected IL-8 synthesis in airway epithelial cell cultures following H. pylori infection. In contrast, inhibition of the p38 MAP kinase pathway (SB203580) resulted in almost complete suppression of H. pylori-induced IL-8 synthesis. Collectively, these results indicate that H. pylori can preferentially elicit IL-8 synthesis in a model of pediatric airway epithelium using the type IV secretion system via p38 MAP kinase.

Airway Microbiome in Different Inflammatory Phenotypes of Asthma: A Cross-Sectional Study in Northeast China

“…Despite various studies have identified the potential protection from the gastrointestinal H. pylori on the allergy of asthma 27 , the research on the immunomodulation of airway epithelium is limited. Colonized H. pylori may participate in the pathogenesis of young asthma by inducing the activation of MAPK p38 protein and the increased production of IL-8, which is tightly associated with the recruitment of neutrophil 28 , 29 . But H. pylori may play a different role in adults' asthma, especially in the different inflammatory phenotypes and needs further investigation.…”

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

“…Although only H.pylori is associated with the activation of E-cadherin/β-catenin/TCF-4 signaling pathway in normal gastric epithelial cells (Yu et al, 2011 , 2014 ), both pathogens are linked to the activation of NF-κβ and MAP kinases oncogenic pathways in GC cell lines (Mohr et al, 2014 ; Liu and Cohen, 2015 ; Byun et al, 2016 ; Dela Pena-Ponce et al, 2017 ). Co-infection by EBV can also hinder the host response to H. pylori .…”

Helicobacter pylori and extragastric diseases

“…Dela Pena‐Ponce et al studied the effect of H. pylori and CagA‐positive strains in a model of pediatric airway epithelium, focusing on the activation of inflammation. Results showed that H. pylori preferentially elicited IL‐8 production via p38 MAP kinase, thus theoretically exhibiting a protective effect in allergic asthma . Similarly, in an animal study, van Wijck et al demonstrated that the administration of an H. pylori extract prior to the allergen challenge on C57BL/6 mice reduced the processing of allergen by dendritic cells in the lungs and mediastinal lymph nodes .…”