Helicobacter pylori Lipopolysaccharide as a Possible Pathogenic Factor for Gastric Carcinogenesis

Abstract

Helicobacter pylori is now recognized as being a causative factor of gastroduodenal diseases such as chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer and gastric low-grade mucosa-associated lymphoma tissue (MALT). Long-term persistent inflammation, injury and reconstitution of gastric mucosa, and immunological reactions against the infected H. pylori are thought to be the causes of lesion formation. Various causative factors of H. pylori for inflammation and injury of gastric mucosa have been proposed. The most studied bacterial pathogenic factors are vacuolating toxin (VacA) produced by H. pylori, ammonium ion generated by H. pylori urease, and monochloramines formed from hypochlorite produced by phagocytic cells and the ammonium ion (Hofman et al., 2004; Xia & Talley, 2001). These agents cause directly injury to the host gastric mucosa. Proinflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor-α (TNF-α), IL-6 and IL-8, are also induced by H. pylori. H. pylori activates the transcription factor NF-κB, which has a key role on inducing various inflammatory reaction including cytokine production, through type IV secretion system (Glocker et al., 1998). The type IV secretion system consisits of proteins encoded by genes located on cag pathogenicity island. In addition, lipopolysaccharide (LPS) is believed to contribute to the pathogenicity of this bacterium. LPS is a major component of Gram-negative bacterial outer membrane. It is known as an endotoxin and is a strong inducer of inflammatory reaction. H. pylori LPS, however, has much lower endotoxic activity than that of other typical Gram-negative bacteria, such as member of the Enterobacteriaceae family (Matsuyama et al., 2001; Muotiala et al., 1992; Nielsen et al., 1994; Perez-Perez et al., 1995; Semeraro et al., 1996). Strong endotoxin at infection sites, such as the systemic circulation system and digestive tract, should lead to sepsis, namely systemic inflammatory response syndrome (SIRS), and severe local inflammation, respectively. The weak endotoxic activity is considered to be important for chronic infection. Weakly endotoxic LPSs are also reported for Chlamydia/Chlamydophila (Heine et al., 2003) and Porphyromonas gingivalis (Ogawa et al., 2000). These bacteria commonly infected humans chronically. Typical LPS acts as a pathogen-associated molecular pattern (PAMP). PAMPs are recognized by pattern recognition receptors (PRRs) of which the most studies are the Toll-