Adhesin HpaA of Helicobacter pylori Promoted Migration of AGS Cells via IL-21 Secretion from HpaA-induced CD4+T Cells

Abstract

Background: As known, there is a high correlation between Helicobacter pylori infection and gastric carcinoma. Objectives: Concerning the important role of adhesin HpaA of H. pylori in the infection process, we aimed to explore whether HpaA promotes gastric cancer metastasis. Methods: In this study, the levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection were compared with post-treatment condition. The levels of IL-21 from CD4+ T cells and culture supernatants with the recombinant HpaA treatment were detected, and then the levels of MMP-2, MMP-9, and metastasis were detected and verified via AGS cells co-cultured with aforesaid CD4+ T cells. Results: Our results showed that higher levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection than without H.pylori infection. Adhesin HpaA induced more IL-21 via CD4+ T cells, and IL-21 induced high MMP-2 and MMP-9 via AGS cells. In particular, HpaA caused this serial reaction to improve the migration of AGS cells, and aptamer HA6 (our previous report) and anti-IL-21 mcAb reduced the above phenomenon remarkably. Conclusions: In summary, our research suggested that adhesin HpaA plays a significant role in the process of gastric carcinoma cell metastasis via IL-21 from HpaA-induced T cells, and aptamer HA6 may be a potential therapeutic agent for H. pylori treatment.

Proteolytic Landscapes in Gastric Pathology and Cancerogenesis

“…ADAM17 proTNF-α [53], TGF-α [44] pro-inflammatory [44,53] response transcriptional repression of the gastric H, K-adenosine triphosphatase α-subunit, reduced acid production [63] MMP1 (collagenase-1) proTNF-α, proIL-1β [42] pro-inflammatory effect [64] MMP2 (gelatinase A) CXCL5 [46] neutrophil recruitment [46], upregulated via IL-21 [48,49] MMP7 (matrilysin-1) proTNF-α [65] HB-EGF [51,54] reduced inflammation, dampens the production of the cytokines [22], immune cells infiltration [24] MMP9 (gelatinase B) CXCL5 [46] neutrophil recruitment [45,46], upregulated via IL-21 [48,49], macrophages infiltration [56], pro-inflammatory and anti-inflammatory activity [64] MMP10 (stromelysin-2) supports bacterial colonization, fosters tissue inflammation, recruitment of T cells [23] Hp0169 Type I collagen colonization of Mongolian gerbils [21] HtrA chronic inflammation [59] Table 1. Cont.…”

“…In return, the resulting tissue microenvironment governs protease production. For instance, the gelatinases MMP2 and -9 are upregulated in a Th17 environment via IL-21 [ 48 , 49 ] and tissue levels of IL-1β are closely linked to MMP3 expression in vivo [ 50 ]. MMP7 production depends on gastrin [ 51 ], which is considered an important mediator of gastric tumorigenesis [ 52 ].…”