Expression of ETS1 in gastric epithelial cells positively regulate inflammatory response in Helicobacter pylori-associated gastritis

Abstract

Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory disorders, including H. pylori-associated gastritis. ETS (E26 transformation specific) transcription factor family is one of the largest families of evolutionarily conserved TFs, regulating critical functions during cell homeostasis. We screened ETS family gene expression in H. pylori-infected mouse and human GECs and found that ETS1 (ETS proto-oncogene 1, transcription factor) expression was highly affected by H. pylori infection. Then, we reported that ETS1 was induced in GECs by H. pylori via cagA activated NF-κB pathway. Notably, we demonstrated that proinflammatory cytokines IL-1β and TNFα have synergistic effects on ETS1 expression during H. pylori infection in an NF-κB-pathway-dependent manner. RNA-seq assay and Gene-ontology functional analysis revealed that ETS1 positively regulate inflammatory response during H. pylori infection. Increased ETS1 is also detected in the gastric mucosa of mice and patients with H. pylori infection. Collectively, these data showed that ETS1 may play an important role in the pathogenesis of H. pylori-associated gastritis.

Helicobacter pylori and its association with autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome

“…H. pylori infection induces a systemic Th-17 inflammatory response, which plays an essential role in the pathophysiology of SLE [ 63 , 64 ]. Moreover, H. pylori can increase the expression of ETS1, through the CagA-activated NF-κB pathway [ 65 ], a negative regulatory transcription factor for Th17 cell and B cell differentiation involved in the pathogenesis of SLE [ 66 ]. Therefore, further investigations are required to comprehend the role of H. pylori in these pathways and the risk of SLE.…”

[Retracted] Clinical Effect of Clarithromycin Combined with Tinidazole on Helicobacter pylori‐Related Gastritis and Its Influence on COX‐2 Expression

“…The gastritis induced by it is chronic and can develop into atrophic gastritis, intestinal metaplasia, and dysplasia. At the same time, cyclooxygenase-2 (COX-2), an important factor in Helicobacter pylori-associated gastritis, angiogenesis, and inhibition of apoptosis in gastric carcinoma are evidently related to infiltration [6][7][8]. Recently, studies have shown that COX-2 expression is upregulated in GC as well as in precancerous lesions and in Helicobacter pylori-induced inflammation, suggesting that COX-2 may play an important role in gastric carcinogenesis [8,9].…”

“…Studies in vitro find that Helicobacter pylori was correlated with an upregulation of the expression of COX-2 mRNA/protein 2 in gastric cancer (GC) cell line. Therefore, the relatively early role of COX-2 in gastric carcinogenesis makes it an attractive target for cancer chemoprevention [6][7][8][9][10][11].…”

A FACT-ETS-1 Antiviral Response Pathway Restricts Viral Replication and is Countered by Poxvirus A51R Proteins

“…Thus, the FEAR pathway appears to both predate and be distinct from, the IFN response. However, only recently was ETS-1 implicated in the host response to microbial infection in bacterial studies where its expression was shown to induced by infection to activate proinflammatory gene expression 30 . Our data indicate that ETS-1 also restricts virus replication and is induced by virus infection in an hSpt16 SUMO /FACT-dependent manner.…”