JOURNAL OF BIOLOGICAL CHEMISTRY
·
2025
·
IF 3.9
Yijun Yang,Nengyi Wang,Yuankun Chen,Tianpeng Ma,Minhua Weng,Haifeng Wu,Qiuping Wu,Yiqiang Xie,Chuanwu Zhu,Wenting Li
Nonalcoholic fatty liver disease (NAFLD) has posed a huge threat to public health globally, but there are currently no approved drugs available. Growing evidence has proved the close association between increased Th17 cells and NAFLD progression. Interleukin-4 induced protein 1 (IL4I1), an amino acid oxidase secreted by immune cells, was reported to regulate the Th17 cells, but its exact role in NAFLD progression has not been fully explained yet. We found that IL4I1 was highly expressed in the liver of C57BL/6J mice with NAFLD induced by an 8-weeks western diet. To explore the IL4I1’s effect, mice were injected with AAV8 encoding IL4I1 1 week before western diet administration. The results showed that IL4I1 overexpression inhibited the NAFLD progression, demonstrated by relieved liver damage and lipid accumulation. The underlying mechanism in which IL4I1 acts on NAFLD might be attributed to the inactivated AKT/forkhead box protein O1 (FOXO1) signaling pathway–mediated decrease of Th17 cells in liver tissues. Subsequently, by culturing naive CD4 + T cells isolated from the spleen of mice in Th17 cell-polarizing conditions, we determined that IL4I1 overexpression inhibited Th17 cell differentiation by inactivating the AKT/FOXO1 pathway, whereas its knockdown exhibited opposite effects. Further, the AKT activator SC79 reversed the effect of IL4I1 overexpression on Th17 cell differentiation. Collectively, our study supports that compensatory upregulation of IL4I1 protects against liver damage and lipid accumulation in NAFLD progression, partially by inhibiting the activated AKT/FOXO1 signaling pathway-induced Th17 cell differentiation.
研究领域:
免疫学
·
肝病学
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分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Xinyu Jiang,Qing Yao,Xing Xia,Yingying Tang,Meng Sun,Yingtao Li,Hailun Zheng,Aimin Cai,Hailin Zhang,Vadivel Ganapathy,Ruijie Chen,Longfa Kou
Psoriasis is a chronic inflammatory skin disease with dysregulation of the immune system, which usually manifests as erythematous scleroma with hyperplasia of the epidermis. Although the pathogenesis remains unclear, oxidative stress and inflammation are inextricably linked during the development of psoriasis. Therefore, scavenging of ROS and suppression of inflammation may be a rational and effective strategy to ameliorate psoriasis and delay its further development. Here, a “Tanghulu”-like nanoplatform (BJN) is developed using the endogenous antioxidant bilirubin and a specific inhibitor (JPH203) of LAT1, an amino acid transporter involved in the activation of mTOR, for treatment of psoriasis by scavenging ROS and interfering with mTOR signaling, consequently blocking Th17 and IL-17 release. The nanoparticles show increased uptake in inflamed keratinocytes and display an efficient ROS scavenging capability. In an in vivo psoriasis model, BJN effectively permeate into the inflamed skin and be retained there, thereby reversing the psoriasis-specific changes in the imiquimod-induced mice as evident from suppression of keratinocyte hyperplasia and decrease in immune cell infiltration. This study shows that BJN can exert a superior anti-psoriasis effect by scavenging ROS, blocking the LAT1-mTOR pathway, inactivating immune reaction, restricting Th17 differentiation, and decreasing IL-17A secretion, offering a promising strategy for psoriasis treatment.
研究领域:
药学
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免疫学
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皮肤病学
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纳米技术
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分子生物学
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Hongyi Li,Yi Wang,Shumin Shao,Hui Yu,Deqin Wang,Chuyuan Li,Qin Yuan,Wen Liu,Jiliang Cao,Xiaojuan Wang,Haibiao Guo,Xu Wu,Shengpeng Wang
Rabdosia serra ( R. serra ), an important component of Chinese herbal tea, has traditionally been used to treat hepatitis, jaundice, cholecystitis, and colitis. However, the chemical composition of R. serra and its effect against colitis remain unclear. In this study, the chemical composition of the water extract of R . serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MS). A total of 46 compounds, comprising ent -kaurane diterpenoids, flavonoids, phenolic acids, and steroids, were identified in the water extract of R . serra , and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length, upregulating anti-inflammatory factors, downregulating proinflammatory factors, and restoring the balance of T helper 17/T regulatory cells. R. serra also preserved intestinal barrier function by increasing the level of tight junction proteins (zonula occludens 1 and occludin) in mouse colonic tissue. In addition, R . serra modulated the gut microbiota composition by increasing bacterial richness and diversity, increasing the abundance of beneficial bacteria ( Muribaculaceae , Bacteroides , Lactobacillus , and Prevotellaceae_UCG-001 ), and decreasing the abundance of pathogenic bacteria ( Turicibacter , Eubacterium_fissicatena_group , and Eubacterium_xylanophilum_group ). Gut microbiota depletion by antibiotics further confirmed that R . serra alleviated colitis in a microbiota-dependent manner. Overall, our findings provide chemical and biological evidence for the potential application of R . serra in the management of colitis.
研究领域:
药理学
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免疫学
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微生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ying-Jie Dong,Yi-Piao Zhang,Xiao-Feng Jiang,Zhi-Yi Xie,Bo Li,Ning-Hua Jiang,Su-Hong Chen,Gui-Yuan Lv
s Background The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. Objectives The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. Methods In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 mL/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16s RNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. Results Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter . Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4 + T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. Conclusions Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4 + T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.
研究领域:
免疫学
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胃肠病学
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药理学
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微生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2022
·Vol. 36
·期 10
·3969-3987
·
IF 6.388
Yi Chen,Shasha Song,Yongfang Wang,Jia Zhu,Xinyu Li
Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.
研究领域:
药理学
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免疫学
·
皮肤科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Qin-wen Gao,Wei-ying Liu,Mirza Jawad,Lei Ci,Yi-yi Cao,Jing Xi,Jia-ying Wu,Yu-yang Lei,Yu-shi Hu,Xin-yue You,Xin-yu Zhang,Jian Fei,Yang Luan
Background Aristolochic acids (AAs)-containing herbs have been used as medicinal remedies for thousands of years. However, exposure to AAI and AAII increases the risk of nephropathy and cancers. Our previous study identified AAIVa, an analogue without carcinogenicity or nephrotoxicity, exerted anti-inflammatory effects. Purpose To explore AAIVa's anti-inflammatory mechanisms and assess its therapeutic potential in arthritis. Methods and Results In this study, we employed in vitro assays on RAW 264.7 cells and explored the underlying mechanisms of AAIVa's anti-inflammatory effect through transcriptome analysis, identifying macrophage polarization-associated genes, IL-17 signaling, and Rheumatoid Arthritis (RA) pathway. Also, we used BALB/cAnSmoc-Zap70 em(W163C)Smoc (SKG)mice, a model that spontaneously develops chronic arthritis closely resembling human RA, and revealed AAIVa's therapeutic potential in arthritis. AAIVa-treatment (10 mg/kg, i.g. ) for 4 weeks protected SKG mice from mannan-accelerated arthritis symptoms, reducing inflammation and improving bone microstructure. We further isolated bone marrow-derived macrophages (BMDMs) and spleen primary cells from SKG and BALB/c mice to evaluate the impact of AAIVa on macrophage polarization and T cell differentiation. We found that AAIVa induced M2 macrophage polarization in BMDMs, and mitigated lipopolysaccharide-stimulated inflammation by increasing Tregs and decreasing Th17 cells. Subsequently, the elevation of M2 macrophages, increased Tregs expression and decreased Th17 cells in the ankle joints of SKG mice supported our in vitro observation. Conclusion We provide first evidence that AAIVa exerts anti-arthritis effects, likely through modulation of macrophage polarization and restoration of the Th17/Treg balance. Our findings highlight AAIVa's mechanism of action and AAIVa's potential as a therapeutic candidate for autoimmune arthritis.
研究领域:
免疫学
·
药理学
·
风湿病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yue Cao,Shouchun Xiao,Bingying He,Xinlei Shi,Nan Xiao,Xueke Liu,Donghui Liu,Zhiqiang Zhou,Peng Wang
Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored the underlying mechanisms based on a mouse model. After 13 weeks of exposure at the acceptable daily intake (ADI) level, fluxapyroxad exacerbated the susceptibility to colitis, impaired the intestinal barrier, and elevated proinflammatory cytokines and chemokines of the colon in mice. It was found that this toxic effect was caused by the disruption of the gut microbiome. Specifically, the abundance of Lachnospiraceae and Muribaculaceae decreased, while Desulfovibrionaceae and Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), and indole-3-acrylic acid (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis by overactivating Th17 cells and insufficient Treg cell differentiation, and causing mild colonic inflammation. Oral antibiotic-treated mice and fecal transfer experiments validated the pathway. Susceptibility to colitis induced by fluxapyroxad was not detected in the oral antibiotic-treated mice. Fecal transfer of the disordered gut microbiota caused by fluxapyroxad could aggravate the severity of colitis in recipient oral antibiotic-treated mice that did not receive fluxapyroxad exposure. In conclusion, chronic fluxapyroxad exposure at the ADI level exacerbated colitis via a gut microbiota–indole derivatives–Treg/Th17 cell balance axis, offering a new risk assessment perspective of fluxapyroxad.
研究领域:
毒理学
·
免疫学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Wang Meng,Li Qiu-Jie,Zhao Hua-Yan,Zhang Jing-Lan
Lethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the activation of NF-κB pathway and decreased the inflammation level of GVHD mice. PKM2 tetramerization blocked Th1 and Th17 cell differentiation and secretion of pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-17). Meanwhile, differentiation of Treg cells and IL-10 secretion were promoted by tetramerized PKM2. These findings demonstrated that PKM2 enhanced the augment of Th1 and Th17 cells to accelerate the progression of GVHD, and allosteric activation of PKM2 targeted Th1 and Th17 cells attenuated GVHD. Furthermore, we also confirmed that TEPP-46 administration did not compromise GVL activity and resulted in slightly improvement of leukemia-free survive. Thus, targeting Th1 and Th17 cell response with PKM2 allosteric activator may be a promising therapeutic strategy for GVHD prevention while preserving the GVL activity in patients receiving Allo-HSCT. Graphical abstract
研究领域:
免疫学
·
血液学
·
移植学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man
Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.
研究领域:
免疫学
·
胃肠病学
·
微生物学
·
药理学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Yue Su,Zhengying Cui,Xinyan Yang,Yujun Jiang,Wei Zhang,Yu Zhang,Chaoxin Man
Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.
研究领域:
微生物学
·
免疫学
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Jianhong Zhou,Xiangxiang Lin,Huiping Shang,Yutuo Zhu,Jinrun Chen,Mengyun Deng,Mali Dai,Dan Lin,Serhii Vakal,Yuqin Wang,Xingyi Li
Noninfectious (autoimmune and immune-mediated) uveitis is one of the primary diseases leading to blindness in the world. Due to the limitation of current first-line drugs for clinical uveitis, novel drugs and targets against uveitis are urgently needed. Ganciclovir (GCV), an FDA-approved antiviral drug, is often used to treat cytomegalovirus-induced retinitis in clinical patients. Recently, GCV was found to suppress neuroinflammation via targeting STING signaling because the STING pathway plays a pivotal role in autoimmune diseases. However, until now, the effect of GCV on non-infectious uveitis has never been explored. In this work, using the rat experimental autoimmune uveitis (EAU) model, we first found STING to be highly expressed in infiltrating cells (CD68 + , CD45 + , and CD4 + ) and retinal glial cells (Iba1 + and GFAP + ) of the immunized retina. More importantly, GCV treatment can significantly suppress the initiation and progression of EAU by inhibiting infiltration of Th17 and inflammatory cells into the retina. Mechanistically, we found that GCV could reverse the levels of pro-inflammatory factors (such as IL-1β) and chemokine-related factors (such as Cxcr3), possibly via targeting the STING pathway. The present results suggest that GCV may be considered as a novel therapeutic strategy against human uveitis.
研究领域:
免疫学
·
眼科学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ming Li,Ru Qu,Ping Li,Xuan Mo,Juan Liu,Biao Dong,Liting Liu,Zhenjiang Zech Xu
This study aimed to investigate the potential alleviating effect of Epimedium polysaccharide (EP) on intestinal inflammation aggravated by Porphyromonas gingivalis (Pg). P. gingivalis , an oral pathogen, may play a role in intestinal inflammation, highlighting the necessity to explore substances capable of inhibiting its pathogenicity. Initially, in vitro screening experiments utilizing co -culturing and quantitative polymerase chain reaction revealed that EP significantly inhibited the growth of P. gingivalis and the levels of virulence genes, including Kgp and RgpA. Subsequent mouse experiments demonstrated that EP notably ameliorated Pg-aggravated weight loss, disease activity index, histopathological lesions, and disruption of intestinal barrier integrity, evidenced by a reduction in tight junction protein levels. Flow cytometry analysis further illustrated that EP attenuated Pg-induced Th17 differentiation and Th17-related cytokines, such as IL-17 and IL-6. Additionally, 16S rRNA amplicon sequencing analysis elucidated that EP significantly mitigated Pg-induced gut microbiota dysbiosis, enriching potentially beneficial microbes, including Akkermansia and Bifidobacterium . The metabolomic analysis provided further insight, indicating that EP intervention altered the accumulation of relevant intestinal metabolites and exhibited correlations with disease indicators. In conclusion, our research suggested that EP holds promise as a prospective therapeutic agent for alleviating P. gingivalis -aggravated intestinal inflammation.
研究领域:
免疫学
·
微生物学
·
药理学
·
胃肠病学
✓ 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）