Effects of Selective Cyclooxygenase‐2 Inhibitor and Non‐Selective NSAIDs on <i>Helicobacter pylori</i>‐Induced Gastritis in Mongolian Gerbils

Bhang, Choon Sang; Lee, Hak Sung; Kim, Sung Soo; Song, Ho-Jun; Sung, Yong Jick; Kim, Sang Hyun; Chung, In Sik; Sun, Hee Sik; Park, Doo Ho; Lee, Youn Soo

doi:10.1046/j.1523-5378.2002.00051.x

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…At 2 or 4 or 8 wks after the bacterial inoculation, gerbils were sacrificed, and gastric mucosal samples were taken for biopsy rapid urease test, microbial culture and histology. H. pylori status was defined as positive if all the three methods gave positive results . A negative H. pylori status was considered if all tests gave concordant negative results.…”

Section: Methodsmentioning

confidence: 99%

“…H. pylori status was defined as positive if all the three methods gave positive results. 26,27 A negative H. pylori status was considered if all tests gave concordant negative results. The remaining stomach samples were collected for immunofluorescence analysis, which was performed on paraffin-embedded gastric tissues by using antibodies against pSTAT3 Tyr705 (1:50), STAT3 (1:200) and TMEFF2 (1:200).…”

Section: Chromatin Immunoprecipitation and Real-time Pcr Quantificatimentioning

confidence: 99%

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Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

Sun

Tang

et al. 2014

Intl Journal of Cancer

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The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.V C 2014 UICC Gastric cancer (GC) is the second leading cause of cancerrelated death worldwide.1 Most patients are diagnosed at an advantaged stage because of lack of early specific symptoms and eventually dead after operation because of recurrence and metastasis. 2,3Helicobacter pylori (H. pylori) is considered as the strongest risk factor among the host genetic and environmental factors influencing the occurrence and progression of GCs. 4,5 H. pylori triggers multiple pathways (JAK/STAT3, NF-jB, PI3K/Akt, Wnt/b-catenin and Ras/Erk) in gastric epithelial

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Section: Methodsmentioning

confidence: 99%

Section: Chromatin Immunoprecipitation and Real-time Pcr Quantificatimentioning

confidence: 99%

Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

Sun

Tang

et al. 2014

Intl Journal of Cancer

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“…However, a few studies failed to confirm the synergistic interaction between NSAIDs and H. pylori infection [35][36][37][38]. Kim [36,37]. In a clinical study conducted by Scheiman et al, rofecoxib, a COX-2 inhibitor, did not significantly affect gastritis scores in patients with H. pylori infection [38].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that genetic deficiency of the COX-1 or COX-2 isoform exacerbated the severity of H. pylori-induced gastritis [23], suggesting that inhibition of COX activity is at least part of the mechanism that NSAIDs exhibit the enhancing effects. However, a few studies failed to confirm the synergistic interaction between NSAIDs and H. pylori infection [35][36][37][38]. Kim et al reported that indomethacin and NS-398 decreased gastric inflammation induced by H. pylori infection in mice [35], while Bhang et al and Magari et al reported that administration of selective COX-2 inhibitors, NS-398, and etodolac did not increase mucosal damage in H. pylori-induced gastritis [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…However, a few studies failed to confirm the synergistic interaction between NSAIDs and H. pylori infection [35][36][37][38]. Kim et al reported that indomethacin and NS-398 decreased gastric inflammation induced by H. pylori infection in mice [35], while Bhang et al and Magari et al reported that administration of selective COX-2 inhibitors, NS-398, and etodolac did not increase mucosal damage in H. pylori-induced gastritis [36,37]. In a clinical study conducted by Scheiman et al, rofecoxib, a COX-2 inhibitor, did not significantly affect gastritis scores in patients with H. pylori infection [38].…”

Section: Discussionmentioning

confidence: 99%

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Effects of Aspirin on the Development of Helicobacter pylori‐Induced Gastric Inflammation and Heterotopic Proliferative Glands in Mongolian Gerbils

Xia

Chen

et al. 2008

Helicobacter

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A positive feedback loop between STAT3 and cyclooxygenase‐2 gene may contribute to Helicobacter pylori‐associated human gastric tumorigenesis

Xiong

Sun

et al. 2013

Intl Journal of Cancer

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Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression both in vitro and in vivo. STAT3 upregulats COX-2 by binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates IL-6=STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX-2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori-positive gastritis tissues exhibited markedly higher levels of pSTAT3Tyr705 than H. pylori-negative ones. High pSTAT3 Tyr705 levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3 Tyr705 may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3=pSTAT3 Tyr705 levels and COX-2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer.

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Effects of Selective Cyclooxygenase‐2 Inhibitor and Non‐Selective NSAIDs on Helicobacter pylori‐Induced Gastritis in Mongolian Gerbils

Cited by 12 publications

References 34 publications

Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

Effects of Aspirin on the Development of Helicobacter pylori‐Induced Gastric Inflammation and Heterotopic Proliferative Glands in Mongolian Gerbils

A positive feedback loop between STAT3 and cyclooxygenase‐2 gene may contribute to Helicobacter pylori‐associated human gastric tumorigenesis

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