Relationship between nuclear factor-kappaB activation and virulence factors of Helicobacter pylori in Japanese clinical isolates.

Abstract

Several factors have been proposed as a possible virulence determinant of Helicobacter pylori infection. The aim of the present study was to evaluate these candidates in nuclear factor (NF)-kappaBeta activation, which is a critical regulator of genes involved in inflammatory reactions. We determined the status of cagE, iceA, HP0441 (a virB4 homolog), the s1 signal sequence of vacA and babA2 by polymerase chain reaction, all of which are candidate virulence determinants, in 107 H. pylori strains isolated from Japanese patients. Nuclear factor-kappaBeta activation was evaluated by the luciferase reporter assay. The gastric mucosa of the hosts was examined histologically. The cagE gene was positive in 102 (95.3%) strains, iceA1 was positive in 71 (66.4%) strains, HP0441 was positive in 68 (63.6%) strains, vacA s1 was positive in 105 (98.1%) strains and babA2 was positive in 103 (96.3%) strains. Nuclear factor-kappaBeta was activated by all cagE-positive strains, but was not activated by any of the cagE-negative strains. The status of iceA or HP0441 was not associated with NF-kappaBeta activation. Neutrophil infiltration in gastric mucosa was significantly more severe in patients infected with cagE-positive strains than in patients infected with negative strains. No association was found between the degree of neutrophil infiltration and the status of HP0441 or iceA. Due to very high positivity of vacA s1 and babA2 in Japanese strains, their roles remain to be investigated. The cag pathogenicity island (PAI) status, as determined by cagE polymerase chain reaction, but not the status of iceA or HP0441, is closely associated with NF-kappaBeta activation and the degree of gastric mucosal inflammation in the hosts.