Infection of mice with H. felis was shown to induce expression of the dual oxidase enzyme complex Duox2/Duoxa2 [51]. Higher colonization rates were observed in Duoxa−/− mice infected with H. felis, compared with WT mice, highlighting the importance of epithelial production of H2O2 as a line of defense against Helicobacter infection. Nfkb1−/− mice developed more pronounced gastric atrophy upon H. felis infection compared with WT mice, while nfkb2−/− mice developed minimal gastric epithelial pathology, and c-Rel-mediated signaling appeared

to modulate the risk of lymphomagenesis [52]. Mesenchymal stem cells were shown to promote an accelerated form of H. felis-induced gastric cancer [53] and their engraftment in chronic inflammation Selleck Venetoclax was shown to be only partially dependent on the CXCR4 receptor.

In H. felis-infected C57BL/6 MEK inhibitor mice, gastric metaplasia coincides with the appearance of CD45+MHCII+CD11b+CD11c+ myeloid cells, which were indeed absent in mice suffering from chronic gastritis without concurrent metaplasia [54]. Deletion in mice of Gli1 inhibited expression of markers of metaplasia, clearly showing that Gli1-dependent myeloid cell differentiation plays a role in the appearance of myeloid cell subtypes required for the development of mucous neck cell metaplasia. In another study, diet-induced obesity in mice was shown to cause an increase in bone marrow-derived immature myeloid cells in blood and gastric tissue of H. felis-infected mice, as well as increased expression of IL-17A, GM-CSF, and STAT3 activation [55]. Not only did obesity promote a protumorigenic gastric microenvironment, but H. felis-induced gastric MCE公司 inflammation also augmented obesity-induced adipose inflammation. Besides an increased intake of fat leading

to obesity, other dietary factors are increasingly recognized as being important factors in modulating progression of Helicobacter-induced gastric pathologies [56]. Partially in contrast to previously published experiments, Yang et al. [57] postulate that bone marrow-derived cells might not be the direct source of gastrointestinal tumor cells induced by H. felis infection. Infection of spontaneously hyperlipidemic mice with H. cinaedi was shown to significantly enhance the development of atherosclerosis [58], with increased expression of proinflammatory genes, accumulation of neutrophils, and induction of macrophage-derived foam cell formation in aortic root lesions. Although infection was asymptomatic, detection of CDT RNA of H. cinaedi indicated an aortic infection. In vitro, H. cinaedi infection altered expression of cholesterol receptors and transporters in macrophages and induced foam cell formation and differentiation of THP-1 monocytes. p16ink4a and p19arf genes are two distinct tumor suppressors located at the Ink4a/Arf locus.