Novel protein antigen (JHP940) from the genomic plasticity region of Helicobacter pylori induces tumor necrosis factor alpha and interleukin-8 secretion by human macrophages

Abstract

The plasticity region of the Helicobacter pylori genome comprises strain-specific gene loci. We performed genotyping and functional biology analysis of one such locus (jhp940) that was previously found to be functionally unknown but present in gastric cancer-associated strains from many different countries. We found its geographic prevalence to be independent of cagA presence and disease status. Cloning, expression, and purification of JHP940 revealed a novel, ∼36-kDa protein in a biologically active form which elicited strong and significant levels of tumor necrosis factor alpha and interleukin-8 in human macrophages. Also, JHP940 was able to induce enhanced translocation of the transcription factor NF-κB complex in cultured macrophages. The induction of the proinflammatory cytokines by JHP940, therefore, points to its putative role in chronic gastric inflammation and, possibly, the various other outcomes of H. pylori infection, including gastric cancer. Copyright © 2008, American Society for Microbiology. All Rights Reserved.