Overexpression of Tim-3 reduces Helicobacter pylori-associated inflammation through TLR4/NFκB signaling in vitro

Wang, Fucai; Mao, Zhirong; Li, Dongsheng; Yu, Jing; Wang, Youhua; Ye, Wen; Lin, Daowei; Zhou, Nan; Xie, Yong

doi:10.3892/mmr.2017.6346

Cited by 16 publications

(11 citation statements)

References 26 publications

(34 reference statements)

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“…Those inflammatory factors can be secreted by gastric epithelial cells and play a major role in triggering the mucosal inflammatory damage caused by H. pylori [44,45]. In addition, H. pylori and its virulence factors are capable of increasing the production of the inflammatory mediators TNF-α, IL-6, and IFN-γ by macrophages, which contribute to the amplification of the inflammatory response in the gastric mucosa [46,47]. In our previous study [17], we demonstrated that L. fermentum UCO-979C significantly reduced the production of IL-8, TNF-α, IL-6, and MCP-1 in AGS cells and macrophages challenged with H. pylori.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, our previous in vitro studies also revealed the ability of the UCO-979C strain to improve the levels of IL-10 in H. pylori-infected macrophages [17], which is in line with the increased concentrations of IL-10 found in gastric and serum samples of H. pylori-infected mice. Increased levels of IL-10 may contribute to the chronicity of gastritis, however, this regulatory cytokine is of fundamental importance to prevent mucosal injury mediated by the inflammatory response [47][48][49][50]. Then, the balance in the inflammatory and regulatory cytokine production induced by L. fermentum UCO-979C could offer advantages in the protection against H. pylori infection, since a reduced inflammatory damage was observed in the histopathological analysis of gastric samples of mice.…”

Section: Discussionmentioning

confidence: 99%

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The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

et al. 2020

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Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

et al. 2020

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“…H. pylori has been described to induce an enhanced M1-like phenotype ( Quiding-Jarbrink et al, 2010 ; Borlace et al, 2011 ; Fehlings et al, 2012 ; Gobert et al, 2014 ; Moyat and Velin, 2014 ), representing the expression of iNOS, which would induce NO to combat H. pylori infection ( Kaparakis et al, 2008 ; Gobert and Wilson, 2016 ; Hardbower et al, 2017 ). M1 macrophages highly express pro-inflammatory cytokines such as IL-1β, IL-6, IL-12p70, TNF-α, and IFN-γ ( Lewis et al, 2011 ; Liao et al, 2016 ; Wang et al, 2017 ; Gebremariam et al, 2019 ). Activation of immune responses by host macrophages upon H. pylori infection requires the involvement of a variety of signaling events such as NF-κB and MAPK ( Gobert and Wilson, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

et al. 2021

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Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.

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“…MyD88 may play a role in gastric immunologic response to H. pylori (29,30). We hypothesized that MyD88 expression correlates with H. pylori infection.…”

Section: Correlation Between Myd88 Expression and H Pylori Infectionmentioning

confidence: 99%

Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China

Chen

Xia

et al. 2020

Front. Oncol.

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Background: Gastric cardia cancer (GCC) arises in the area of the stomach adjoining the esophageal-gastric junction and has unique risk factors. It was suggested that the involvement of Helicobacter pylori is associated with GCC from high-risk population. Myeloid differentiation factor 88 (MyD88) is a crucial adaptor molecule in Toll-like signaling pathway recognizing H. pylori. Its role in GCC has not been elucidated yet. In this study, our purpose is to investigate the expression and significance of MyD88 in GCC tissue. Methods: Expression of MyD88 and nuclear factor κB (NF-κB) p105/p50 and infection of H. pylori were detected by immunohistochemistry in gastric cardia tissue. The correlation of MyD88 expression to NF-κB p105/p50 expression, H. pylori infection, and clinicopathologic characteristics in gastric cardia tissue was analyzed. The involvement of MyD88 in patient prognosis was also analyzed. Results: Our data showed that the expression of MyD88 elevated from normal mucosa to inflammation (p = 0.071). The expression of MyD88 was enhanced in GCC tissues by contrast to non-malignant cardia mucosa (p = 0.025). What's more, overexpression of MyD88 was detected in intestinal-type adenocarcinoma with inflammation. Patients with high MyD88 staining revealed a better differentiation (p = 0.02). MyD88 also positively correlated with NF-κB p105/p50 expression (p = 0.012) in cancer tissue. Expression of MyD88 was increased but not significantly in biopsies with H. pylori infection compared with non-infected biopsies. Multivariate analyses revealed lymph node metastasis but not MyD88 expression was an independent predictor for patient survival. Conclusion: These findings provide pathological evidence that upregulating MyD88 and inducing inflammation might be involved in gastric cardia carcinogenesis in high-risk population. MyD88 plays a role in gastric cardia carcinogenesis with NF-κB pathway activation. Higher MyD88 expression is not a major prognostic determinant in GCC, but it may relate to the tumor cell differentiation.

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Overexpression of Tim-3 reduces Helicobacter pylori-associated inflammation through TLR4/NFκB signaling in vitro

Cited by 16 publications

References 26 publications

The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China

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