Frontiers in Neuroscience
·
2022
·
IF 5.152
Yan-Lin Chen,Lan Bai,Dilirebati Dilimulati,Shuai Shao,Che Qiu,Ting Liu,Shuo Xu,Xue-Bing Bai,Lin-Juan Du,Lu-Jun Zhou,Wen-Zhen Lin,Xiao-Qian Meng,Yi-Chao Jin,Yan Liu,Xiao-Hua Zhang,Sheng-Zhong Duan,Feng Jia
Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17 + γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4 + T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.
研究领域:
神经科学
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免疫学
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微生物学
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病理学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 7
·e70539
·
IF 4.2
Yingjie Shen,Yitong Zhou,Kuziwakwashe Alice Chiwa,Junxin Wang,Shihong Ren,Mingxuan Wang,Hongru Ren,Yeyi Zheng,Ying Yu,Lutao Jiang,Jingmou Yu,Yuchun Qiao,Litai Jin,Jianlin Lou,Xiangkuo Zheng
Psoriasis is an immune-mediated inflammatory dermatological disorder characterized by the interaction between immune cells and keratinocytes, which perpetuates cutaneous inflammation and cellular hyperproliferation. In this study, we identified a strong δ-catenin signature in psoriatic skin; however, the precise role of δ-catenin remains to be elucidated. Additionally, we observed that Interleukin (IL)-17A, a pivotal cytokine involved in the development of psoriatic lesions, induces δ-catenin expression in HEKn and HACAT cells. From a mechanistic perspective, δ-catenin initiated NF-κB signaling, subsequently leading to the activation of IL-6 and IL-8 production. Furthermore, silencing δ-catenin expression mitigated IL-17A-induced hyperproliferation of keratinocytes through the NF-κB pathway. Our study further identified miR-101 and miR-122 as upstream regulators of δ-catenin, exerting their effects by downregulating δ-catenin protein levels. We demonstrated that miR-101 and miR-122 can inhibit the hyperproliferation of keratinocytes induced by δ-catenin. These findings validate the role of δ-catenin in the pathogenesis of psoriasis, particularly in keratinocyte-mediated inflammatory responses and cellular hyperproliferation. Consequently, miR-101 and miR-122 hold potential as therapeutic agents in the treatment of psoriasis. Graphical The schematic diagram delineates the signaling pathway associated with IL-17A-induced psoriasis, highlighting the upregulation of delta-catenin, which initiates NF-κB signaling. This activation subsequently leads to the production of IL-6 and IL-8, as well as the hyperproliferation of keratinocytes. Furthermore, miR-101 and miR-122 function as inhibitors of delta-catenin, effectively obstructing this signaling cascade.
研究领域:
皮肤病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2025
·
IF 4.9
Meiling She,Tianbai Li,Lingli Zhou,Zihao Deng,Minna Huang,Yan Yan,Meng Zhang,Yajun Yang,Dongtao Wang
Background Sarcopenia significantly impairs quality of life, especially in diabetic patients, where effective treatment options remain limited. The IL-17a-related gut-muscle axis suggests a potential role of the gut microbiota in the development of sarcopenia. Ursolic acid (UA) has shown promise as an anti-sarcopenic agent. Nevertheless, the relationship between UA and the IL-17a-related gut-muscle axis remains unclear. Methods In this research, sarcopenia model was established using streptozotocin in vivo and in vitro with TNF-α-managed C2C12 myotubes. Results UA significantly altered the gut microbiota, notably increasing observed OTUs and the Shannon index of sarcopenic mice. Specifically, UA effectively mitigated the decrease of Bacteroides thetaiotaomicron and restored the total level of short-chain fatty acids, particularly reducing propionic acid and increasing isovaleric acid. Additionally, UA markedly improved muscle quality and function, as evidenced by increased body weight, grip strength, and muscle weight, as well as significantly decreased expression of Atrogin-1 and MuRF-1. Moreover, RNA sequencing results clearly indicated that UA suppressed the IL-17 signaling pathway in sarcopenic mice. Furthermore, UA alleviated oxidative stress and apoptosis in sarcopenic mice. Notably, UA inhibited the IL-17a pathway in sarcopenic mice by suppressing the heightened expression of the proteins. In vitro experiments further confirmed that UA inhibited TNF-α-induced myotube atrophy, reduced Atrogin-1 and MuRF-1 expression, and strongly suggested that IL-17a may be a key target of UA in combating myotube atrophy. Conclusions The study emphasizes the importance of UA in alleviating sarcopenia, possibly through the IL-17a-related gut-muscle axis.
研究领域:
药理学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2014
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IF 3.18
Haili Qi,Hang Yang,Gang Xu,Jingli Ren,Wei Hua,Yingpeng Shi,Malvin Torsvik,Jon Florholmen,Guanglin Cui
Chronic inflammation increases colorectal cancer (CRC) risk as seen in ulcerative colitis (UC). Proinflammatory cytokines play a critical role in mediating the development of colitis associated cancer (CAC). In this study, the therapeutic efficacy of anti-interleukin (IL)-17A by anti-IL-17A antibody injection on the development of CAC was assessed in 1,2-dimethylhydrazine (DMH) plus dextran sulfate sodium (DSS) induced CAC mouse model. The results showed that mice dosed with DMH plus DSS for 10 weeks evoked high degree dysplastic lesion in the large bowel that accompanied with significant increased IL-17A expression, proliferation index and inflammation degree in mice. After anti-IL-17A antibody injection for 2 weeks, the number of tumors, proliferation index and the expression level of IL-17A protein in the large bowel tissues were significantly decreased. Therefore, we concluded that the anti-IL-17A blockade can suppress the development of CAC and is a potential therapeutic agent for the prevention of CAC in colitis mice.
研究领域:
肿瘤学
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免疫学
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消化病学
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DOI
PubMed
高影响因子
Nano Today
·
2024
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IF 13.2
Qiaoxuan Wang,Qi Cheng,Guangshuai Yao,Zhaolong Wang,Lingjiang Zhu,Zhiru Zeng,Lingyun Jia,Yan Du,Jing Xue,Changyou Gao
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease primarily driven by inappropriate infiltration and activation of immune cells and pro-inflammatory cytokines. Among them, neutrophils with high plasticity play a pathogenic role in RA by abnormal neutrophil immune activities. As anti-IL-17A therapies failed to achieve long-term ideal therapeutic outcomes in clinical trials, we speculated that the underlying cause may be associated with the abnormal activity of neutrophils that have a direct link to IL-17A. Herein, we created a cationic hydrogel loaded with anti-IL-17A nanobodies (Nbs) capable of synergistically weakening the inflammatory activities of neutrophils and relieving inflammation in RA. Based on the host-guest interaction, the hydrogel was comprised of β-cyclodextrin-modified hyperbranched polylysine (HBPL-CD) and adamantane-modified hyaluronic acid (HA-Ad). The physical properties were adjusted to match the mechanical environment of joints and enable injection. The hydrogel with Nbs could adsorb cell-free DNA (cfDNA) persistently and slowly release anti-IL-17A Nbs, which synergistically alleviated the inflammatory activities of neutrophils via inhibiting the IL-17A stimulated neutrophil extracellular traps (NETs) of neutrophils from RA patients and mice with collagen-induced arthritis (CIA), reducing the level of pro-inflammatory cytokines, and suppressing the inflammatory phenotype of neutrophils in vitro . The ankle injection of the hydrogel with Nbs into a mouse model of CIA could alleviate the RA symptoms in vivo . This novel platform is believed to provide a guideline for treating IL-17A-related diseases by combining Nbs with the immunoregulation of neutrophils.
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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风湿病学
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DOI
高影响因子
PLoS One
·
2023
·Vol. 18
·期 2
·e0281845
·
IF 3.7
Hao Tang,Shida Zhu,Kai Chen,Shujie Yuan,Junzu Hu,Hongkai Wang
Bone is a frequent target of tumor metastasis, with high incidence rate and poor prognosis. Osteoclasts play a key role in the process of tumor bone metastasis. Interleukin-17A (IL-17A) is an inflammatory cytokine, highly expressed in a variety of tumor cells, that can alter the autophagic activity of other cells, thereby causing corresponding lesions. Previous studies have shown that low concentration IL-17A can promote osteoclastogenesis. The aim of this study was to clarify the mechanism of low concentration IL-17A promoting osteoclastogenesis by regulating autophagic activity. The results of our study showed that IL-17A could promote the differentiation of osteoclast precursors (OCPs) into osteoclasts in the presence of RANKL, and increase the mRNA levels of osteoclast-specific genes. Moreover, IL-17A increased the expression of Beclin1 by inhibiting the phosphorylation of ERK and mTOR, leading to enhanced autophagy of OCPs, accompanied by decreased OCP apoptosis. Furthermore, knockdown of Beclin1 and suppression of autophagy by 3-methyladenine (3-MA) significantly attenuated the enhanced osteoclastogenesis induced by IL-17A. In summary, these results indicate that low concentration IL-17A enhances the autophagic activity of OCPs through the ERK/mTOR/Beclin1 pathway during osteoclastogenesis, and further promotes osteoclast differentiation, suggesting that IL-17A may serve as a potential therapeutic target for cancer-related bone resorption in cancer patients.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Infection and Drug Resistance
·
2023
·
IF 3.9
Lingna Xu,Ren-ai Xu,Dan Zhang,Shanshan Su,Hanyan Xu,Qing Wu,Yuping Li
Background: T helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methods: Six to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.Results: The proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).Conclusion: The expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.
研究领域:
免疫学
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微生物学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
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IF 7.6
Xiang Li,Jie Yang,Erbao Shi,Yiguang Lu,Xiaochao Song,Huifeng Luo,Jundong Wang,Chen Liang,Jianhai Zhang
Fluoride is widely found in groundwater, soil, animal and plant organisms. Excessive fluoride exposure can cause reproductive dysfunction by activating IL-17A signaling pathway. However, the adverse effects of fluoride on male reproductive system and the mechanisms remain elusive. In this study, the wild type and IL-17A knockout C57BL/6J mouse were treated with 24 mg/kg·bw·d sodium fluoride and/or 5 mg/kg·bw·d riboflavin-5′-phosphate sodium for 91 days. Results showed that fluoride caused dental fluorosis, increased the levels of ROS in testicular Leydig cells and GSSG in testicular tissue, and did not affect the iron and serum hepcidin levels in testicular tissue. Riboflavin alleviated above adverse changes, whereas IL-17A does not participate in the oxidative stress-mediated reproductive toxicity of fluoride. Based on this, TM3 cells were used to verify the injury of fluoride on Leydig cells. Results showed that fluoride increased mRNA levels of ferroptosis marker SLC3A2 , VDAC3 , TFRC , and SLC40A1 and decreased Nrf2 mRNA levels in TM3 cells. The ferroptosis inhibitor Lip-1 and DFO were used to further investigate the relationship between male reproductive toxicity and ferroptosis induced by fluoride. We found that the fluoride-induced decrease in cell viability, increase in xCT, TFRC, and FTH protein expression, and decrease in GPX4 protein expression, can all be rescued by Lip-1 and DFO. Similar results were also observed in the riboflavin treatment group. Moreover, riboflavin mitigated fluoride-induced increases in ROS levels and SLC3A2 protein levels. In all, our work revealed that riboflavin inhibited ferroptosis in testicular Leydig cells and improved the declined male reproductive function caused by fluoride. This study provides new perspectives for revealing new male reproductive toxicity mechanisms and mitigating fluoride toxicity damage.
研究领域:
毒理学
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生殖生物学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2024
·Vol. 23
·期 1
·1-15
·
IF 3.9
Guo XiaoYu,Zhou Jianglu,Yu Hong,Cao Han,Li Xia,Hu Qing,Yu YunQiu
Background Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography–mass spectrometry (GC–MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC–MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis. Methods The established in situ derivatization method for analysing LCFAs with a GC–MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out ( Tcrd −/− ) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients. Results A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC–MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd −/− mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly. Conclusions This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd −/− mice.
研究领域:
皮肤病学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Yingpei Miao,Shuqing Yu,Qingcui Zhang,Xiaomei Li,Bowei Xia,Li Yang,Xiaobin Li,Junwei He
Leonurus japonicus Houtt. (LJ) is a pivotal traditional Chinese medicine remedy for thrombosis; however, its potential mechanisms and active constituents remain unclear. In this study, LJ exhibits a significant antithrombotic effect on an arteriovenous bypass thrombosis rat, characterized by reductions in thrombus wet and dry weights, decreased maximum aggregation rate, increased thrombus formation inhibition rate, aggregation inhibition rate, alterations in fibrinogen and antithrombin III levels, and shortened coagulation indicators. Moreover, LJ significantly enhanced the erythrocyte staining area and intensity in an arachidonic acid-induced zebrafish heart. Network pharmacology indicated that LJ alleviates thrombosis by regulating TNF and IL-17 pathways. Metabolomics revealed that LJ significantly modulated 29 endogenous differential metabolites, linking it to the regulation of primary bile acid biosynthesis, IL-17, and TNF pathways. Zebrafish experiments and molecular docking suggested that kaempferol and apigenin exhibit antithrombotic effects by modulating TNF and IL-17 proteins. Finally, molecular dynamics simulation validated that kaempferol and apigenin have strong binding capabilities with TLR4, STAT3, TNF-α, and IL-17A, and their binding free energies are −20 to −27 and −13 to −15 kcal/mol, respectively. In conclusion, LJ exerts its antithrombotic effect by regulating lipid metabolism and inhibiting TLR4/STAT3/TNF-α/IL-17A pathways, with kaempferol and apigenin identified as bio-constituents. This plant holds significant potential for development and utilization in antithrombotic therapies. Graphical This study is the first to integrate network pharmacology, rat model, metabolomics, zebrafish model, molecular docking, and MD simulation techniques to elucidate the anti-thrombotic effect and mechanism of Leonurus japonicus by modulating lipid metabolism and inhibiting TLR4/STAT3/TNF-α/IL-17A pathways, with kaempferol and apigenin identified as primary pharmacological constituents.
研究领域:
药理学
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中医药学
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心血管疾病
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系统生物学
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计算生物学
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动物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2025
·
IF 3.7
Chenmei Peng,Pan Lei,Hongying Qi,Qianjun Zhu,Chushun Huang,Ju Fu,Chengyu Zhao
Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a “virtual organ” can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A–mTOR–HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A–mTOR–HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.
研究领域:
医学
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免疫学
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微生物学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 11
·1-10
·
IF 5.3
Li Xiaoqing,Huang Feng,Bao Chengqi,Shao Rong,Deng Lei,Yang Minghui
The overexpression of interleukin-17A (IL-17A) is closely associated with the pathogenesis of autoimmune diseases and cancer, rendering precise identification of IL-17A level critical for disease diagnosis and prognosis monitoring. In this study, CsPbBr 3 nanoclusters (NCs) were embedded in C 16 H 14 Br 2 O 6 Pb 2 organometallic compound (Pb-MA MOC) via a hot injection approach. Through this way, the issue of CsPbBr 3 NCs susceptible to decomposition in water was solved, and the photocurrent intensity that is generated by CsPbBr 3 was significantly enhanced. A highly sensitive photoelectrochemical (PEC) sensor for detecting IL-17A in human serum was developed using CsPbBr 3 /Pb-MA as the photoactive material. The electrode was initially modified with CsPbBr 3 /Pb-MA. Then, antibody-modified Fe 3 O 4 magnetic nanoparticles (MNs) with target analyte IL-17A captured, and IL-17A antibody-modified Au@CuNi diatomic catalyst (DAC) formed sandwich immune complex structure on the electrode. The existence of CuNi DAC led to a substantial reduction in photoelectric signal intensity due to oxidation of ascorbic acid in the supporting electrolyte. The photocurrent intensity exhibited linear correlation with IL-17A concentration within the range 15-750 pg/mL, and achieving an impressive detection limit of 1 pg/mL. Moreover, the sensor was successfully applied to the determination of IL-17A in human serum, suggesting its potential clinical applications. Graphical Abstract
研究领域:
生物医学工程
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分析化学
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纳米技术
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免疫学
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临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）