Helicobacter pylori and N-Methyl-N’-nitro-N-nitrosoguanidine Induction of Dendritic Cell Infiltration of the Pyloric Mucosa of Mongolian Gerbils

Abstract

The dendritic cell is not only an antigen-presenting cell, it is immunologically resistant to stomach carcinogenesis induced by the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). We have demonstrated that the mRNA expression of major histocompatibility complex (MHC) class II-associated invariant chain (Ii), which is produced in mature dendritic cells, is markedly enhanced by treatment with MNNG, and it was more enhanced in a carcinogen-resistant strain (Buffalo) than a sensitive strain (ACI). This suggests that the dendritic cell may play a key role in carcinogenic resistance. Helicobacter pylori is supposed to be a promoter of gastric cancer, and its infection causes massive dendritic cell infiltration. We have demonstrated that interferon-γ (IFNγ) may be an important player in resistance to carcinogenesis based on H. pylori-infected mongolian gerbil experiments. A group of 80 mongolian gerbils were divided into 16 groups and were treated with or without H. pylori and MNNG. Their pyloric mucosa mRNA was extracted for the reverse transcriptase-polymerase chain reaction. IFNγ mRNA expression was enhanced by MNNG treatment and H. pylori infection and was similar to that of Ii. On the other hand, the pattern of OX-62 (a dendritic cell marker expressed in mature or immature cells) was rarely enhanced by MNNG, and it was not like the Ii pattern. The different patterns for Ii and OX-62 suggest that INFγ, which is manufactured by MNNG-treated epithelial cells and is a stimulator of dendritic cell maturation, may play a key role in resistance to carcinogenesis.