Molecular Medicine Reports
·
2021
·Vol. 24
·期 6
·1-9
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IF 2.952
Juanjuan Huang,Xianfeng Chen,Aihua Xie
Formononetin has proven to be anti‑inflammatory and able to alleviate symptoms of certain allergic diseases. The present study aimed to determine and elucidate the potential effects of formononetin in allergic rhinitis. JME/CF15 cells were pretreated with formononetin at different doses, followed by stimulation with IL‑13. Cell Counting Kit‑8 assay was performed to determine the cytotoxicity of formononetin. The expression levels of inflammation‑related proteins, histamine, IgE, TNF‑α, IL‑1β, IL‑6, granulocyte‑macrophage colony‑stimulating factor and eotaxin in IL‑13‑stimulated JME/CF15 cells were detected using ELISAs. The expression levels of phosphorylated‑NF‑κB p65, NF‑κB p65 and cyclooxygenase‑2 (Cox‑2) were analyzed using western blotting. Reverse transcription‑quantitative PCR, western blotting and immunofluorescence were performed to measure the levels of mucin 5AC oligomeric mucus/gel‑forming. Expression levels of sirtuin 1 (SIRT1) and nuclear erythroid factor 2‑related factor 2 (Nrf2) proteins were also measured using western blotting. The results of the present study revealed that formononetin exerted no cytotoxic effect on the viability of JME/CF15 cells. Following stimulation of JME/CF15 cells with IL‑13, formononetin suppressed the upregulated expression levels of proinflammatory cytokines. IL‑13‑induced formation of mucus was also attenuated by formononetin treatment. Furthermore, it was found that the SIRT1/Nrf2 signaling pathway was activated in formononetin‑treated JME/CF15 cells, whereas treatment with the SIRT1 inhibitor, EX527, reversed the effects of formononetin on IL‑13‑induced inflammation and mucus formation in JME/CF15 cells. In conclusion, the findings of the current study indicated that formononetin may activate the SIRT1/Nrf2 signaling pathway, thereby inhibiting IL‑13‑induced inflammation and mucus formation in JME/CF15 cells. These results suggested that formononetin may represent a promising agent for the treatment of allergic rhinitis.
研究领域:
免疫学
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药理学
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细胞生物学
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过敏
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产品关联
DOI
PubMed
高影响因子
IMMUNOLOGY
·
2021
·Vol. 164
·期 2
·292-304
·
IF 7.397
Yanbiao Shi,Meizhen Xu,Shuai Pan,Sijia Gao,Jinfeng Ren,Ruixue Bai,Hui Li,Cheng He,Shuli Zhao,Zhixu Shi,Fang Yu,Zou Xiang,Hui Wang
Allergic diseases are caused by dysregulated Th2 immune responses involving multiple effector cells including basophils. Short chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, exert immunomodulatory functions via activation of its receptors GPR41 and GPR43, and inhibition of the histone deacetylases (HDACs) activity. In allergic diseases, SCFAs suppress the activity of mast cells, eosinophils and type 2 innate lymphoid cells (ILC2) but enhance the function of Th2 cells. Here, we aimed to elucidate the function of SCFAs on human basophils. Human basophils were purified from healthy donors by flow cytometric sorting. The surface proteins, apoptosis and degranulation of basophils were analyzed by flow cytometric analysis. The mRNA expression was assayed using real-time PCR. Interleukin 4 (IL-4) and IL-13 were measured by ELISA. Histone acetylation was examined by western blot. GPR41 was expressed by basophils and was enhanced by IL-3. Acetate induced intracellular calcium influx in basophils which was suppressed by blocking GPR41. Propionate and butyrate, but not acetate, induced the expression of CD69 and IL-13. In addition, propionate and butyrate enhanced IgE-mediated basophil degranulation but inhibited basophil survival and IL-4 secretion. Propionate and butyrate induced histone acetylation of basophils and suppression of HDACs activity mimicked the effects of propionate and butyrate on human basophils. Our findings demonstrate that propionate and butyrate may play a complex role in regulating basophil apoptosis, activation and degranulation via inhibiting HDACs activity. The in vivo effects of SCFAs on the regulation of basophil-associated allergic diseases need to be further explored.
研究领域:
免疫学
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过敏
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 5
·2416-2431
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IF 6.1
Jianming Liu,Na Yang,Xingcheng Yi,Guoqiang Wang,Cuizhu Wang,Hongqiang Lin,Liwei Sun,Fang Wang,Dongdong Zhu
Increasing studies have demonstrated that ginsenoside Rg3 (Rg3) plays an important role in the prevention and treatment of various diseases, including allergic lower airway inflammation such as asthma. To investigate the role of Rg3 in allergic upper airway disease, the effect and therapeutic mechanism of Rg3 in allergic rhinitis (AR) were studied. Ovalbumin-induced AR model mice were intragastrically administered with Rg3. Nasal symptoms, levels of IgE, IL-4, IL-5, IL-13, SOD and MDA in serum, and histopathological analysis of nasal mucosa were used to evaluate the effect of Rg3 on ameliorating AR in mice. Moreover, nasal mucosa samples from the normal control group, AR model group and high dosage of Rg3 were collected to perform omics analysis. The differentially expressed genes and significantly changed metabolites were screened based on transcriptomics and metabolomics analyses, respectively. Integrative analysis was further performed to confirm the hub genes, metabolites and pathways. After Rg3 intervention, the nasal symptoms and inflammatory infiltration were effectively improved, the levels of IgE, IL-4, IL-5, IL-13 and MDA were significantly reduced, and the level of SOD was obviously increased. The results of the qRT-PCR assay complemented the transcriptomic findings. Integrated analysis showed that Rg3 played an anti-AR role mainly by regulating the interaction network, which was constructed by 12 genes, 8 metabolites and 4 pathways. Our findings suggested that Rg3 had a therapeutic effect on ovalbumin-induced AR in mice by inhibiting inflammation development and reducing oxidative stress. The present study could provide a potential natural 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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转录组学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LARYNGOSCOPE
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2022
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IF 2.97
Tiancong Liu,Yang Sun,Zhaohui Guo,Weiliang Bai
Objectives Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. Study design In vivo and in vitro. Methods We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). Results CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4 + /GATA3 + Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of β-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. Conclusions CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. Level of Evidence NA Laryngoscope , 2022
研究领域:
免疫学
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分子生物学
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过敏
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呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biology Direct
·
2024
·
IF 5.7
Hao Wang,Lei Zhang,Yunxiao Shang
Endoplasmic reticulum (ER) stress has been shown to play a pivotal role in the pathogenesis of asthma. DEPTOR (DEP Domain Containing MTOR Interacting Protein) is an endogenous mTOR inhibitor that participates in various physiological processes such as cell growth, apoptosis, autophagy, and ER homeostasis. However, the role of DEPTOR in the pathogenesis of asthma is still unknown. In this study, an ovalbumin (OVA)-induced mice model and IL-13 induced 16HBE cells were used to evaluate the effect of DEPTOR on asthma. A decreased DEPTOR expression was shown in the lung tissues of OVA-mice and IL-13 induced 16HBE cells. Upregulation of DEPTOR attenuated airway goblet cell hyperplasia, inhibited mucus hypersecretion, decreased the expression of mucin MUC5AC, and suppressed the level of inflammatory factors IL-4 and IL-5, which were all induced by OVA treatment. The increased protein expression of ER stress markers GRP78, CHOP, unfolded protein response (UPR) related proteins, and apoptosis markers in OVA mice were also inhibited by DEPTOR overexpression. In IL-13 induced 16HBE cells, overexpression of DEPTOR decreased IL-4, IL-5, and MUC5AC levels, preventing ER stress response and UPR process. Furthermore, from the proteomics results, we identified that SOD1 (Cu/Zn Superoxide Dismutase 1) may be the downstream factor of DEPTOR. Similar to DEPTOR, upregulation of SOD1 alleviated asthma progression. Rescue experiments showed that SOD1 inhibition abrogates the remission effect of DEPTOR on ER stress in vitro. In conclusion, these data suggested that DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1.
研究领域:
免疫学
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肺病学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
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2023
·Vol. 24
·期 4
·1-15
·
IF 3.3
Wang Yaru,Shang Yunxia,Tang Fengyu,Qiu Kun,Wei Xiaohui,Wang Zhengtao
In this work, self-double-emulsifying drug delivery system enteric-coated capsules (PNS-SDE-ECC) were used to enhance the oral bioavailability and anti-inflammatory effects of Panax notoginseng saponins (PNS), which are rapidly biodegradable, poorly membrane permeable, and highly water-soluble compounds. The PNS-SDEDDS formulated by a modified two-step method spontaneously emulsified to W/O/W double emulsions in the outer aqueous solution, which significantly promoted the absorption of PNS in the intestinal tract. The release study revealed that PNS-SDE-ECC exhibited sustained release of PNS within 24 h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3 months. Furthermore, compared to PNS gastric capsules, the relative bioavailability of NGR1, GRg1, GRe, GRb1, and GRd in PNS-SDE-ECC was increased by 4.83, 10.78, 9.25, 3.58, and 4.63 times, respectively. More importantly, PNS-SDE-ECC significantly reduced OXZ-induced inflammatory damage in the colon by regulating the expression of TNF-α, IL-4, IL-13, and MPO cytokines. Overall, the prepared PNS-SDE-ECC may serve as a viable vehicle for increasing the oral bioavailability of PNS and its anti-inflammatory action on ulcerative colitis. Graphical Abstract
研究领域:
药剂学
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药理学
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药物递送系统
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2021
·
IF 4.407
Yu-bo Sun,Mo Liu,Xin-sheng Fan,Li-ping Zhou,Meng-wen Li,Fang-yuan Hu,Qin-fei Yue,Yi-ming Zhang
The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1 −/− ) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1 −/− -OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1 −/− -OVA group and TRPA1 −/− -OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.
研究领域:
免疫学
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呼吸病学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry and Cell Biology
·
2022
·Vol. 101
·期 1
·
IF 3.73
Guihua Song,Suping Yu,Yan Zhang,Mengmeng Sun,Bingxue Zhang,Minghao Peng
Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.
研究领域:
免疫学
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药理学
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呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
BMC Pharmacology & Toxicology
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2024
·Vol. 25
·期 1
·1-12
·
IF 2.8
Tian Chunyan,Liu Qi,Zhang Xiaoyu,Li Zhuying
Background Calycosin, a flavonoid compound extracted from Astragalus membranaceus , has shown anti-asthma benefits in house dust mite-induced asthma. Recent studies have suggested that innate-type cells, including group 2 innate lymphoid cells (ILC2s) and macrophages, serve as incentives for type 2 immunity and targets for drug development in asthma. This work focuses on the effects of calycosin on the dysregulated ILC2s and macrophages in allergic asthma. Methods In vivo, the asthmatic mouse model was established with ovalbumin (OVA) sensitization and challenge, and calycosin was intraperitoneally administered at doses of 20 and 40 mg/kg. In vivo, mouse primary ILC2s were stimulated with interleukin (IL)-33 and mouse RAW264.7 macrophages were stimulated with IL-4 and IL-13 to establish the cell models. Cells were treated with calycosin at doses of 5 and 10 µM. Results In vivo, we observed significantly reduced numbers of eosinophils, neutrophils, monocyte macrophages and lymphocytes in the bronchoalveolar lavage fluid (BALF) of OVA-exposed mice with 40 mg/kg calycosin. Histopathological assessment showed that calycosin inhibited the airway inflammation and remodeling caused by OVA. Calycosin markedly decreased the up-regulated IL-4, IL-5, IL-13, IL-33, and suppression tumorigenicity 2 (ST2) induced by OVA in BALF and/or lung tissues of asthmatic mice. Calycosin repressed the augment of arginase 1 (ARG1), IL-10, chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1) levels in the lung tissues of asthmatic mice. In vivo, calycosin inhibited the IL-33-induced activation as well as the increase of IL-4, IL-5, IL-13 and ST2 in ILC2s. Calycosin also repressed the increase of ARG1, IL-10, YM1 and MRC1 induced by IL-4 and IL-13 in RAW264.7 macrophages. In addition, we found that these changes were more significant in 40 mg/kg calycosin treatment than 20 mg/kg calycosin. Conclusions Collectively, this study showed that calycosin might attenuate OVA-induced airway inflammation and remodeling in asthmatic mice via preventing ILC2 activation and macrophage M2 polarization. Our study might contribute to further study of asthmatic therapy.
研究领域:
免疫学
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药理学
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呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jiankun Guan,Yuxin Wu,Xin Liu,Huimin Wang,Ningbing Ye,Zheng Li,Chen Xiao,Zhijie Zhang,Zifu Li,Xiangliang Yang
Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT–SS–NLG919 (CN) and its nanoformulation [email protected] ( [email protected] ), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and [email protected] promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-β, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation [email protected] are promising candidates for the treatment of intractable TNBC.
研究领域:
肿瘤学
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药理学
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免疫学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhao Ze Qiang,Chen Bo Zhi,Gan Jia Li,Feng Yun Hao,Liang Ling,Yu Lingyun,Wang Zi Yi,Abbaszadeh Samin,Shahbazi Mohammad-Ali,Yu Ruixing,Guo Xin Dong
Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of autoimmunity. However, the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune psoriasis. In this project, we introduce a dual-functional microneedle (DF-MN) designed to combine MNs with multiple release kinetics and immunotherapy, the programmed treatment is achieved through segmented design of the MN structure, realizing the unification of rapid and long-lasting treatment of autoimmune psoriasis. In vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues, whereas HA@IL-13 showed minimal fluorescent signals after 2 days. The multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level, in combination with coarse-grained molecular dynamics. Additionally, DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model, suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.
研究领域:
生物医学工程
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免疫学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
INFLAMMATION
·
2023
·
IF 5.1
Feng Yong,Hu Jiapeng,Liu Fen,Shang Yunxiao
Asthma is a chronic inflammatory disease characterized by airway remodeling and lung inflammation. Collagen triple helix repeat containing 1 (CTHRC1), a glycoprotein, is involved in multiple pathological processes, including inflammation and fibrosis. However, the function of CTHRC1 in asthma remains unclear. In the present study, the mouse asthma model was successfully generated by sensitizing and challenging mice with ovalbumin (OVA). CTHRC1 expression at both RNA and protein levels was significantly upregulated in lung tissues of asthmatic mice. Asthmatic mice exhibited significant airway remodeling as evidenced by increased bronchial wall and smooth muscle cell layer thickness, goblet cell hyperplasia and collagen deposition, and epithelial-mesenchymal transition (EMT), but those characteristics were reversed by CTHRC1 silencing. The cell model with transforming growth factor-β1 (TGF-β1) induction in bronchial epithelial cells (BEAS-2B) was conducted to verify the effects of CTHRC1 on EMT, a classic mechanism that mediates airway remodeling. The results showed that TGF-β1 stimulation increased CTHRC1 expression, and CTHRC1 knockdown inhibited TGF-β1-induced EMT. OVA-treated mice also showed increased inflammatory cell infiltration and the production of OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-5, and IL-13, which were decreased by CTHRC1 downregulation. The effects of CTHRC1 on OVA-induced airway inflammation were further determined by treating BEAS-2B cells with IL-13, in which CTHRC1 knockdown reduced the IL-13-induced secretion of pro-inflammatory factors, including IL-4 and IL-5. In conclusion, these results indicate that CTHRC1 silencing attenuates asthmatic airway remodeling and inflammation in vivo and in vitro, suggesting that CTHRC1 may be a potential target for asthma treatment. Graphical Abstract
研究领域:
免疫学
·
呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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