Tangeretin promotes regulatory T cell differentiation by inhibiting Notch1/Jagged1 signaling in allergic rhinitis

Xu, Shunqing; Kong, Yonggang; Jiao, Wo-Er; Yang, Rui; Qiao, Yue-Long; Xu, Yu; Tao, Zezhang; Chen, Shi‐Ming

doi:10.1016/j.intimp.2019.04.039

Cited by 34 publications

(20 citation statements)

References 40 publications

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“…Previous study believed that the imbalance of Th1/Th2 cells was the predominant pathogenesis of AR [ 27 ]. Recently, Th17/Treg cells sharing the same precursor cell (CD4 + T cells) as Th1/Th2 cells were discovered to be typically unbalanced during allergic inflammation [ 28 ]. Th17 cells induced by a Th2 cytokine (IL-6) are recognized as a pivotal player in modulating autoimmune response and combating bacterial infections [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, increased IgE level was discovered to indicate a high severity of AR [ 44 , 45 ]. Xu et al’s study showed that generation of OVA-induced IgE was repressed, while FOXP3/Treg cell differentiation was promoted by tangeretin administration [ 28 ]. In accordance with these findings, our study demonstrated conspicuously up-regulated levels of ROR-γt, IL-17 as well as IgE in serum of AR mice, whereas CGA application repressed the up-regulated levels of these indices in AR mice.…”

Section: Discussionmentioning

confidence: 99%

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Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells

et al. 2020

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Allergic Rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking Th17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possess anti-viral, anti-inflammatory, and anti-bacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone. The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological of nasal mucosa were conducted by hematoxylin-eosin staining and periodic acid-schiff staining. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, qRT-PCR, or western blot. The ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosal of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells

et al. 2020

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“…However, in our study, the activation level of the NOTCH1 signaling pathway did not differ betweenearly and advanced stage patients. Previous studies suggested that NOTCH1 can induce Th2 cell differentiation [17,18]. The NOTCH-Th2 differentiation pathway was upregulated in early stage patients.…”

Section: Discussionmentioning

confidence: 91%

“…6D). Previous studies have suggested that NOTCH1 can induce Th2 cell differentiation [17,18]. Gene signatures were derived from KEGG and are shown in Table S1.…”

Section: Notch1 Mutation In Advanced Stage Samples Reduced Th2 Cell Dmentioning

confidence: 99%

Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

Li¹,

Liu²,

Zhou³

et al. 2021

Preprint

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Background: Tongue squamous cell carcinoma (TSCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on TSCC remains unclear.Methods: Transcriptome data and somatic mutation data of TSCC were obtained from the HNSC project of The Cancer Genome Atlas (TCGA). Immune filtration analysis between early stage (clinical stage I–II) and advanced stage (III–IV) was performed using single-sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed genes were filtered and their related functions were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Kaplan-Meier survival analysis and a Cox-regression model were used to evaluate the survival of patients with the CCL22 signature. Maftools was used to show an overview of somatic mutations in TSCC. Results: In patients with TSCC, Th2 cells were significantly increased in patients in the early stage of the disease. The Th2 cell-related chemokine CCL22 was downregulated in patients in the advanced stage. Univariate and multivariate Cox analyses revealed CCL22 as a good prognostic factor for TSCC. A nomogram based on the expression of CCL22 was constructed as a prognostic indicator for TSCC. NOTCH1 mutation was increased in patients in the advanced stage, which inhibited activation of the NOTCH1-Th2 differentiation pathway.Conclusions: In TSCC, high expression of CCL22 can promote the recruitment of Th2 cells and predict better survival. Mutation of NOTCH1 inhibits the differentiation of Th2 cells. Combined with decreased Th2 cell recruitment and differentiation, tumor progression may occur.

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“…[64]. e anti-inflammatory effect of tangeretin has been reported in different pathological conditions such as allergic rhinitis via stimulating regulatory T cell [65], asthma by regulating phosphoinositide 3-kinase (PI3K) pathway [21], and Respiratory Syncytial Virus-induced inflammation by curbing NF-κB and interleukin-1 beta (IL-1B) [23]. Furthermore, tangeretin alleviated cisplatin-induced renal inflammation via inhibiting NF-κB activation and decreasing its downstream IL-1B and TNF-α [66], as well as iNOS and TNF-α during reinstatement of the anti-inflammatory interleukin-10 (IL-10) [67].…”

Section: Tangeretin In Inflammationmentioning

confidence: 99%

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Arafa

Shurrab

Buabeid

2021

Advances in Pharmacological and Pharmaceutical Sciences

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Chemotherapeutics can induce oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and abnormalities in neurotransmitter metabolism leading to toxicity. Because there have been no therapeutic strategies developed to target inflammation and oxidative stress, there is a continuing need for new and improved therapy. As a result, there has been increasing interest in complementary and alternative medicine with anticancer potential. Studies have shown that the antioxidant activities and anti-inflammatory effects of citrus fruits are promising natural phytochemicals in the development of new anticancer agents. Tangeretin is a naturally polymethoxylated flavone compound extracted from the citrus peel that has shown significant intestinal absorption and adequate bioavailability, with the added benefit of promoting longevity. In addition, tangeretin is known to exhibit considerable selective toxicity to many types of cancer cell proliferation such as ovarian, brain, blood, and skin cancer. Evidence indicates that tangeretin acts through several mechanisms including growth inhibition, induction of apoptosis, autophagy, antiangiogenesis, and estrogenic-like effects. Furthermore, tangeretin works through mitigating levels of inflammatory mediators in the immune system. Using tangeretin in combination with clinically applied anticancer drugs could be a good strategy for increasing the efficiency of these agents and protecting noncancerous cells from damage caused by chemotherapy. The purpose of this review is to highlight the protective effects of a novel natural product, tangeretin against chemotherapeutic-induced toxicity. The development of chemoprevention strategies can lead to significant health care improvement in cancer survivors. Thus, study outcomes may attract more investigators to conduct tangeretin-related research and find out potentially significant impacts on health care of cancer patients and decreased health problems associated with chemotherapeutics-induced toxicity.

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Tangeretin promotes regulatory T cell differentiation by inhibiting Notch1/Jagged1 signaling in allergic rhinitis

Cited by 34 publications

References 40 publications

Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells

Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells

Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

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