Helicobacter pylori secreted peptidyl prolyl cis, trans-isomerase drives Th17 inflammation in gastric adenocarcinoma
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Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer.
KeywordsGastric cancer Helicobacter pylori Pathogenesis Cytokines Th17 VEGF Matrix metalloproteinase
This work was supported by Italian Ministry of University and Research Grant 2008C33HRL_003, the Italian Ministry of Health and the Istituto Superiore di Sanità (to M.M.D.E.), the Indian Council of Medical Research, Government of India (to M.K.) and Progetto di Eccellenza Fondazione Cassa di Risparmio di Padova e Rovigo and Associazione Italiana per la Ricerca sul Cancro Grant Regionale 2008 (to M.d.B.).
Conflict of interest
The authors have no financial conflict of interest.
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