INFLAMMATION
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2025
·Vol. 49
·期 1
·13
·
IF 5
Xiaoxu Ding,Hui Su,Tiancong Liu,Yu Chen,Zhao Gao,Ziwen Chang,Weiliang Bai
Allergic rhinitis (AR) is an inflammatory disease of the upper airway that primarily affects the nasal mucosa, with Th2 differentiation-driven inflammation as a key contributor. A bioinformatics analysis of dataset GSE52804 identified Six-transmembrane epithelial antigen of prostate 4 (STEAP4), a metalloreductase involved in inflammation regulation, as associated with AR progression, though its specific function remains unclear. Data obtained from nasal mucosal tissues from AR patients ( n = 13) and an ovalbumin (OVA)-induced AR mouse model demonstrated a marked upregulation of STEAP4. Subsequent loss-of-function experiments revealed that STEAP4 knockdown reduced Th1/Th2 imbalance-mediated inflammation, alleviating allergic symptoms in OVA-treated mice. Further investigations involved the purification of naïve CD4 + T cells from healthy murine splenocytes and their Th2 polarization. Consistently, STEAP4 knockdown inhibited Th2 differentiation and the production of Th2-related cytokines in vitro. Additionally, Guanine adenine thymine adenine sequence-binding protein 3 (GATA3), a transcription factor essential for Th2 differentiation, was predicted to bind to the STEAP4 promoter. CHIP-PCR and dual-luciferase assays confirmed the transcriptional regulation of STEAP4 by GATA3. More importantly, STEAP4 knockdown rescued the promoting effects of GATA3 overexpression on Th2 differentiation. In conclusion, STEAP4 functions downstream of GATA3 to promote AR development by promoting Th2 differentiation-mediated inflammation, suggesting its potential as a target for AR treatment.
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BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 85
·期 8
·1809-1817
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IF 2.043
Li Qiang,Zhai Chunmiao,Wang Guodong,Zhou Jia,Li Weiguang,Xie Liquan,Shi Zhanli
Ginsenoside Rh1 (Rh1) has anti-inflammatory effects in asthma mice, but the underlying mechanism remains unclear. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to construct asthma model. Mice received Rh1 or tiotropium bromide 0.5 h before OVA challenge. Airway morphology and airway remodeling were assessed by HE staining and Masson's trichrome staining, respectively. Th1/Th2 cytokines in serum or broncho alveolar lavage fluid (BALF) were measured by ELISA kits. Rh1 significantly alleviated the lung resistance and airway resistance, and reduced the number of total inflammation cells, eosinophils, neutrophils, and lymphocytes in BALF of the asthmatic mice. The morphological changes and collagen deposition of airway were also reduced by Rh1 in asthmatic mice. The increase of Eotaxin, IL-4, IL-5, IL-13, and IL-33 and the decrease of IL-12 and IFN-γ in both BALF and serum of OVA exposed mice were reversed by Rh1. Rh1 attenuates OVA-induced asthma in the mice model by regulating Th1/Th2 cytokines balance.
研究领域:
免疫学
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药理学
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呼吸病学
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CELL BIOLOGY INTERNATIONAL
·
2017
·Vol. 41
·期 6
·611-621
·
IF 1.831
Yaojie Niu,Qiumei Dong,Rongheng Li
To investigate the efficacy and mechanisms of matrine, a component derived from Sophora flavescens in treatment of rheumatoid arthritis (RA), a rat model of RA was established. Compared to control rats, matrine significantly mitigated inflammation and severity of RA (paw volume and articular index (AI) score). Using either mice splenic T cells stimulated with PMA/ionomycin or rat splenic T cells, the levels of Th1 and Th2 responses were determined by flow cytometry, quantitative RT-PCR, and ELISA. Furthermore, the levels of NF-κBp65 (RelA), IκBα, and phosphor-IκBα in T cells were determined by Western blot. Our study found that matrine modulated the imbalance of Th1 and Th2 cytokine responses in rats with RA by reducing the levels of Th1 cytokines (IFN-γ, TNF-α, IL-1β), but increasing Th2 cytokine (IL-4 and IL-10) through attenuating the NF-κB signaling in T cells, suggesting matrine as a promising drug for intervention of RA.
研究领域:
免疫学
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药理学
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风湿病学
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ACS Omega
·
2023
·
IF 4.1
Zhihai Wu,Zhiqiang Luo,Wen Sun,Yuanyuan Shi,Qi Ding
Allergic asthma is a prevalent form of asthma that is characterized primarily by airway inflammation. Jiegeng decoction (JGT) is a traditional Chinese herbal formula known for its anti-inflammatory properties and has been used to treat respiratory diseases for centuries. This study aimed to investigate the biological effects and mechanisms of action of JGT in improving allergic asthma. An experimental allergic asthma mouse model was established using ovalbumin. The results showed that JGT significantly improved inflammation cell infiltration in the lung tissue of allergic asthmatic mice and the inflammatory environment of Th2 cells in the bronchoalveolar lavage fluid while also reducing serum IgE levels. Subsequently, 38 components of JGT were identified through liquid chromatography–mass spectrometry. Network pharmacology revealed that regulating inflammation and immune responses is the primary biological process by which JGT improves allergic asthma, with Th2 cell differentiation and the JAK-STAT signaling pathway being the key mechanisms of action. Finally, qPCR, flow cytometry, and Western blotting were used to validate that JGT inhibited Th2 cell differentiation by blocking the JAK1-STAT6 signaling pathway in CD4+ T cells, ultimately improving allergic asthma. This study provides a novel perspective on the therapeutic potential of JGT in the treatment of allergic asthma.
研究领域:
药理学
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免疫学
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中医
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分子生物学
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BMC BIOLOGY
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2024
·Vol. 22
·期 1
·1-17
·
IF 4.4
Yang Yuxuan,Li Wenqing,Sun Kaineng,Sun Siyu,Zhang Yong,Chen Lin,Ni Yangyue,Hou Min,Xu Zhipeng,Chen Lu,Ji Minjun
Background Inflammatory bowel disease (IBD), a persistent gastrointestinal disease, is featured with impaired gut immunity. Previous studies have demonstrated that tuft cells can regulate the intestinal type 2 immune response by activating downstream ILC2 and Th2 cells and repair gut barrier upon invasion of parasitic helminths, bacteria, protozoans, and enteritis through different chemo-sensing receptors, such as bitter taste receptors. Berberine is a widely used in the treatment of diarrhea in clinic, however the mechanism underlying this effect is not clear. In this study, we aim to explore the relationship between berberine and tuft cells in dextran sulfate sodium (DSS) -induced colitis.Results Our data showed that berberine significantly ameliorated DSS-induced colitis and regulating type 2 innate immune lymphocytes (ILC2) and Th2 immune cells via tuft cells in the gut. Furthermore, the effect of berberine on colitis was partially abolished by U73122, a bitter taste receptor inhibitor, suggesting that bitter taste signalling pathway played an important role in the effect of berberine on relieving colitis.Conclusion sBerberine ameliorates dextran sulfate sodium -induced colitis through tuft cells and bitter taste signalling. Our study reveals the unique pharmacological mechanisms of berberine in the context of colitis, laying the foundation for further clinical applications of this compound.
研究领域:
药理学
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免疫学
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胃肠病学
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JOURNAL OF ETHNOPHARMACOLOGY
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2018
·
IF 3.115
Wenhao Xu,Meiqun Hu,Qihong Zhang,Jingbo Yu,Weike Su
Ethnopharmacological relevance Cassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough (‘pertussis’) and inflammatory diseases . Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma. Aim of the study To explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma. Materials and methods Extraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN- γ ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2 -ΔΔCt method. Results Treatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN- γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. Conclusions These findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.
研究领域:
药理学
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免疫学
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民族药理学
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呼吸医学
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PHYTOMEDICINE
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2021
·
IF 5.34
Xiaohan Wei,Baoping Zhang,Xiao Liang,Changshun Liu,Ting Xia,Yingjie Xie,Xue Deng,Xiaomei Tan
ABSTRACT Background Allergic rhinitis (AR) is an inflammatory, immunoglobulin E (IgE)-mediated disease characterized by the typical symptoms of sneezing, rhinorrhea , nasal itching , and congestion. Higenamine (HG) is a plant-based alkaloid, possesses a wide range of activities, including vascular and tracheal relaxation, antioxidative, antiapoptotic , anti-inflammatory, and immunomodulatory activities. So far, the effect and the underlying mechanism of HG on AR have not been studied. Hypothesis/Purpose The purpose of this study was to evaluate the effects of HG on AR and investigate its underlying mechanism. Methods The effects of HG on AR were evaluated in an ovalbumin-induced AR mouse model. Network pharmacology-based methods such as target prediction, protein-protein interaction (PPI) network analysis, pathway analysis, and molecular docking were used to identify the likely HG targets. Finally, we validated the mechanism of action of HG through its effects on these targets in human nasal epithelial cells (HNEpCs). Results Oral administration of 30, 60, and 120 mg/kg HG significantly alleviated rubbing and sneezing in AR mice and attenuated histopathological changes in the lung and nasal tissues . Additionally, HG reduced the levels of IgE, histamine, and IL-4 in the serum of AR mice, and regulated imbalance in Th1/Th2 cells. Using network pharmacology-based methods, we identified 29 HG targets related to AR. These targets are mainly involved in the PD-L1, relaxin, estrogen, HIF-1, Th1 and Th2 cell differentiation , T cell receptor , and the Th17 cell differentiation signaling pathways . Molecular docking showed that HG may well be suited to the receptor binding pockets of key target AKT1 , EGFR, c-Jun, NOS2 , and JAK2 . In HNEpCs, HG inhibited the histamine-induced mRNA expression and secretion of interleukin (IL)-6, and IL-8, as well as the expression of MUC5AC and the phosphorylation of NF-κB. Moreover, HG affected the changes of AKT1, EGFR, c-Jun, iNOS, and JAK2 induced by histamine. Conclusion Overall, our results suggest that HG may alleviate AR by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling. HG, therefore, has great potential as a therapeutic agent for the treatment of AR.
研究领域:
免疫学
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药理学
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分子生物学
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细胞生物学
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Oncotarget
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2017
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IF 5.168
Zhe Cheng,Ling-Ling Dai,Xi Wang,Liu-Qun Jia,Xiao-Gang Jing,Peng-Fei Li,Meng Liu,Huan Wang,Lin An
This study aims to explore how microRNA-145 (miR-145) affects airway remodeling and cytokine expression by targeting epidermal growth factor receptor (EGFR) to regulate mucin 5AC (MUC5AC). Mice alveolar epithelial cells (AECs) were divided into a control, blank, miR-145 mimics, mimic control, miR-145 inhibitors, inhibitor control, si- EGFR and miR-145 inhibitors + si- EGFR group. Asthma mice models with airway remodeling were induced with an Ovalbumin (OVA) solution and randomly divided into a normal, asthma, asthma + miR-145 mimics, asthma + miR-145 mimic control, asthma + si- EGFR or asthma + si- EGFR NC group. Airway remodeling degree and histomorphology was measured using hematoxylin-eosin (HE), Masson and periodic acid-Schiff (PAS) staining. Flow cytometry was used to detect Th2 and Th17 cells in peripheral blood, ELISA was used to measure inflammatory factors. qRT-PCR and western blotting was adapted to detect the expressions of EGFR and the relevant cytokines that are regulated by miR-145. The control, miR-145 mimics and si- EGFR groups showed a higher expression of miR-145 and a lower expression of EGFR and cytokines than the blank, mimic control, inhibitor control and miR-145 inhibitor + si- EGFR groups. Mice in the asthma + miR-145 mimics and asthma + si- EGFR groups showed lower WAt/Pbm, WAi/Pbm and WAm/Pbm, less inflammatory cells, less airway modeling and alleviated goblet cell hyperplasia and mucus obstruction than the asthma group. Furthermore, the expressions of EGFR and cytokines of transfected cells and lung tissues were negatively related to those of miR-145. MiR-145 can down-regulate MUC5AC by negatively targeting EGFR and thereby relieving airway remodeling.
研究领域:
分子生物学
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呼吸医学
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免疫学
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Food Science and Human Wellness
·
2024
·
IF 5.6
Yanan Liu,Huan Li,Chong Wang,Shanjun Chen,Renjie Lian,Weiqiang Wang,Linglin Fu,Yanbo Wang
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk. However, its influences on immunological components, especially the function of key immune cells, are still poorly known. In this work, we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells, dendritic cells, and T cells. The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine. Moreover, it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells, especially those related to allergy. At the same time, the proportion of MHC class II-positive dendritic cells and the proportion of T helper 2 (Th2) cells in CD4 + T cells increased after histamine stimulation. We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines, disrupt the balance of the immune homeostasis, and potentially lead to adverse immune reactions. This work demonstrated the importance of including the estimation of histamine's immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
研究领域:
免疫学
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食品科学
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毒理学
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高影响因子
CLINICAL AND EXPERIMENTAL ALLERGY
·
2021
·Vol. 52
·期 1
·46-58
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IF 5.018
Nan Wang,Jue Wang,Yongjing Zhang,Shiling Hu,Tianxiao Zhang,Yuanyuan Wu,Xiuzhen Sun,Tao Zhang,Shuanying Yang,Langchong He
Background Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. Objective We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. Methods We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Results Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice. Conclusions & clinical relevance Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs. Graphical Here, we found that SP levels were increased in the serum samples of patients with asthma, which was independently associated with the risk of asthma. In mice model, SP induced lung peribronchial inflammation, fibrosis, and glycogen deposition, with high levels of Th2-related cytokines in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice, which indicated that SP induced Th2 lung inflammation in mice was dependent on MCs.
研究领域:
免疫学
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肺科学
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过敏学
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分子生物学
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Cancer Communications
·
2023
·
IF 16.2
Shujie Chen,Lina Fan,Yifeng Lin,Yadong Qi,Chaochao Xu,Qiwei Ge,Ying Zhang,Qiwen Wang,Dingjiacheng Jia,Lan Wang,Jianmin Si,Liangjing Wang
Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis ( B.a ) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. Methods Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143 + CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. Results We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed Apc Min/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143 + CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha + B cells in TME. CD143 + CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/β-catenin signaling in CD143 + CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143 + CAFs predicted the better survival outcome in CRC patients. Conclusions These results highlighted that B.a induced a new subset of CD143 + CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.
研究领域:
癌症生物学
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微生物学
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分子生物学
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细胞生物学
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免疫学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
·
IF 6.953
Teng Wang,Chen Shen,Feng Guo,Yuqin Zhao,Jie Wang,Kunlai Sun,Bin Wang,Yan Chen,Yin Chen
A polysaccharide, CSL-0.1, was isolated from the medicinal lichen, Usnea longissima . CSL-0.1 was a neutral rhamnose-containing glucogalactomannan with a molecular weight of 7.86 × 10 4 Da. The polysaccharide had a core mannan structure with (1 → 6)-α- d -Man p units as the main chain and was substituted at the O -2 positions with side chains containing (1 → 2)-α- d -Man p residue, [3)-α-Glc p (1 → 4)-α-Glc p (1→] and 6- O -substituted β- d -Gal f units. 2- O - and 2,3-di- O -substituted Rha p units. The effects of CSL-0.1 on intestinal immunity and antioxidant activity were evaluated. CSL-0.1 increased the spleen and thymus indices in a dose-dependent manner and conferred immunomodulation on reversing the Th1/Th2-related cytokine imbalance in cyclophosphamide (CP)-induced immunosuppressed mice. CSL-0.1 could also enhance the levels of secretory immunoglobulin A in CP-injected mice. Additionally, the antioxidant levels in the liver and intestine of the mice were increased 20%–50% after intragastric injection by CSL-0.1.
研究领域:
免疫学
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药理学
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生物化学
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药物化学
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危险品化学品经营许可证（带存储）