Expression of TLR1, TLR3 and TLR7 genes remarkably down-regulated from erosion to peptic ulcer and gastric cancer development

Shirafkan, Fatemeh; Shokri‐Shirvani, Javad; Morakabati, Payam; Alhooei, Saman; Pirzadeh, Marzieh; Barari, Ladan; Hamidian, Seyed Mohammad Taghi; Cherati, Mina Rezaee; Rajabnia, Ramazan; Nouri, Hamid Reza

doi:10.1016/j.genrep.2021.101229

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…Pre-treatment with BIEE effectively inhibited the increase of TLR-4, reduction of IL-1β expression via suppressing of NF-κB. Downregulation of TLR4 plays a vital role in gastric ulcer healing [ 50 ]. Based on various studies, anti-inflammatory action is crucial for preventing peptic ulcers [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway

El-Gendy

Taher²,

Elgamal

et al. 2023

Antioxidants

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Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers’ progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1β and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1β and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI–Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

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Section: Discussionmentioning

confidence: 99%

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway

El-Gendy

Taher²,

Elgamal

et al. 2023

Antioxidants

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“…TLR7 expression was favorably linked with the infiltration of DCs, macrophages, neutrophils, and T lymphocytes. 293 Furthermore,TLR7 expression was shown to be significantly higher in erosive gastric tissue specimens as compared with controls and to be significantly lower as the disease advanced to gastric cancer, according to Shirafkan et al 294 Acute inflammation was significantly impacted by the early disease phase elevation in TLR7 expression, but not chronic inflammation. TLR7 downregulation may, via many pathways, contribute to the development of GC.…”

Section: Tlr7mentioning

confidence: 96%

“…TLR7 downregulation may, via many pathways, contribute to the development of GC. 294 Wang et al 295 synthesized a GC vaccine by covalently linking a TLR7 agonist to the GC antigen MG7-Ag quadruple epitope, which inhibited gastric tumor growth and immune tolerance. Ma et al 296 constructed a bifunctional small hairpin RNA (shRNA) vector containing a Bcl-2 silencing shRNA and TLR7-stimulated ssRNA, and stimulation with this bifunctional vector in vitro promoted significant apoptosis in mouse gastric cancer cells and inhibited subcutaneous gastric cancer cell growth in vivo by regulating the expression of apoptosis-related proteins and inducing the release of IFNs.…”

Section: Tlr7mentioning

confidence: 99%

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Toll‐like receptors in health and disease

Wang,

Huang,

Zhan

et al. 2024

MedComm

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Toll‐like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation‐related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR‐related diseases.

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Immunological Strategies in Gastric Cancer: How Toll-like Receptors 2, -3, -4, and -9 on Monocytes and Dendritic Cells Depend on Patient Factors?

Kos,

Bojarski,

Mertowska

et al. 2024

Cells

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(1) Introduction: Toll-like receptors (TLRs) are key in immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In gastric cancer (GC), TLR2, TLR3, TLR4, and TLR9 are crucial for modulating immune response and tumor progression. (2) Objective: This study aimed to assess the percentage of dendritic cells and monocytes expressing TLR2, TLR3, TLR4, and TLR9, along with the concentration of their soluble forms in the serum of GC patients compared to healthy volunteers. Factors such as disease stage, tumor type, age, and gender were also analyzed. (3) Materials and Methods: Blood samples from newly diagnosed GC patients and healthy controls were immunophenotyped using flow cytometry to assess TLR expression on dendritic cell subpopulations and monocytes. Serum-soluble TLRs were measured by ELISA. Statistical analysis considered clinical variables such as tumor type, stage, age, and gender. (4) Results: TLR expression was significantly higher in GC patients, except for TLR3 on classical monocytes. Soluble forms of all TLRs were elevated in GC patients, with significant differences based on disease stage but not tumor type, except for serum TLR2, TLR4, and TLR9. (5) Conclusions: Elevated TLR expression and soluble TLR levels in GC patients suggest a role in tumor pathogenesis and progression, offering potential biomarkers and therapeutic targets.

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Expression of TLR1, TLR3 and TLR7 genes remarkably down-regulated from erosion to peptic ulcer and gastric cancer development

Cited by 3 publications

References 23 publications

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway

Toll‐like receptors in health and disease

Immunological Strategies in Gastric Cancer: How Toll-like Receptors 2, -3, -4, and -9 on Monocytes and Dendritic Cells Depend on Patient Factors?

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