IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2023
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IF 3.3
Xiulian Zhang,Xueliang Li,Wei Ma,Fangying Liu,Pinxian Huang,Lei Wei,Li Li,Yechang Qian
Background Chronic obstructive pulmonary disease (COPD) has a high fatality rate and poses a great threat to human health. Astragaloside IV (AS-IV) is proven to attenuate cigarette smoke (CS)-induced pulmonary inflammation, based on which this research focuses on the mechanism of AS-IV in COPD.Methods To evaluate the effects of AS-IV, CD4+ T cells received different concentrations of AS-IV. CD4+ T cell viability, T helper 17 (Th17)/regulatory T (Treg) markers and CXCR4 expressions in CD4+ T cells or spleen/lung tissues were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction and Western blot. The proportions of Treg and Th17 cells were assessed by flow cytometry. Enzyme-linked immune sorbent assay was employed to determine cytokine contents in serum and lung tissues.Results AS-IV with concentration exceeding 40 µM inhibited CD4+ T cell viability. In vitro, AS-IV suppressed the expressions of CXCR4, retinoid-related orphan receptor γt (RORγt), and interleukin (IL)-17A as well as Th17 cells but promoted the expressions of forkhead box p3 (Foxp3) and IL-10 as well as Treg cells, while CXCR4 overexpression reversed the effects of AS-IV. In vivo, AS-IV alleviated COPD, and CS-induced Th17/Treg imbalance in mice and reduced CS-induced down-regulation of IL-10 in serum and lung tissues and Foxp3 and up-regulation of IL-1β, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A in serum and lung tissues and RORγt. AS-IV mitigated CS-induced CXCR4 up-regulation. Above effects of AS-IV on mice were offset by CXCR4 overexpression.Conclusions AS-IV restores Th17/Treg balance via impeding CXCR4 to ameliorate COPD.
研究领域:
免疫学
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肺科学
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药理学
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DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Hongtao Zhu,Zhi-Jing Ni,Qian Zhong,Wei Wang,Ya-Jing An,Kiran Thakur,Jian-Guo Zhang,Zhong-Li Chen,Zhao-Jun Wei
The bio-functional activities of sericin, a silk protein, have been explored across various fields, underscoring its potential therapeutic applications due to anti-inflammatory, antioxidant, and wound-healing effects. Sericin has also been shown to ameliorate ulcerative colitis (UC). While previous studies have noted the effects of intact sericin on ameliorating UC to some extent, there remains a significant gap in understanding the mechanism of action of small molecule sericin peptide (SRP). In this study, we explored the therapeutic efficacy of SRP in a dextran sulfate sodium (DSS)-induced mouse model of UC. Various oral doses of SRP were administered, and their effects were assessed through a range of physiological and biochemical parameters associated with UC. Our findings demonstrated that SRP effectively alleviated UC symptoms, as evidenced by improved physiological indices and reduced inflammatory markers. Additionally, transcriptomic and proteomic analyses revealed that the beneficial effects of SRP on UC were linked to the regulation of key biological pathways, particularly those involved in Th17 cell differentiation. To further validate our data, Western-blot, and immunofluorescence assays verified that SRP modulates Th17 cell differentiation, alleviating inflammation and maintaining homeostasis within the colonic vascular environment. Furthermore, SRP treatment was shown to protect colonic mucosal function, contributing to the overall improvement in UC symptoms. By regulating Th17 cell differentiation and modulating inflammatory pathways, SRP presents a promising approach to managing UC and enhancing mucosal health.
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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分子生物学
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DOI
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2016
·Vol. 120
·期 6
·560-570
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IF 3.097
Hongjun Zhang,Baoling Ju,Xiaoli Zhang,Yanfei Zhu,Ying Nie,Yuanhong Xu,Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis , which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo . In response to ConA stimulation, the CD4 + T cells preferred to polarizing towards CD4 + T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA-treated liver in addition to suppressing interleukin (IL)-17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α-SMA) and desmin. More transforming growth factor (TGF)-β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro , the recombinant IL-17A plus TGF-β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up-regulated phospho-Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell-mediated fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
研究领域:
免疫学
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微生物学
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药理学
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呼吸医学
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DOI
PubMed
高影响因子
FASEB JOURNAL
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2017
·Vol. 31
·期 4
·1756-1766
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IF 5.498
Haijie Liu,Chunxiao Wan,Yanan Ding,Ranran Han,Yating He,Jinting Xiao,Junwei Hao
Experimental autoimmune neuritis (EAN) is a CD4 + T-cell–mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T-helper (T h )17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4 + T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed T h 17-cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome. —Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing T h 17-cell differentiation and regulating cytokine production. FASEB J . 31, 1756–1766 (2017) www.fasebj.org
研究领域:
免疫学
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神经病学
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药理学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Yu Zhang,Wenting Ji,Hailong Qin,Zehong Chen,Yinxing Zhou,Zhihong Zhou,Jinglin Wang,Kaiping Wang
Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.
研究领域:
胃肠病学
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Asthma and Allergy
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2022
·
IF 3.027
Yang Sun,Tiancong Liu,Weiliang Bai
Purpose This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). Patients and Methods Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 μg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×10 7 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 μg OVA from day 21 to 27. Results The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4 + T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. Conclusion MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.
研究领域:
免疫学
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2023
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IF 2.4
Jinxia ZHU,Hongxiu CHEN,Jianjiao CUI,Xiaorui ZHANG,Guangwei LIU
Autoimmune hepatitis (AIH) is a kind of autoimmune disease mediated by T cells, and its incidence is gradually increasing in the world. Oroxylin A (OA) is one of the major bioactive flavonoids that has been reported to inhibit inflammatory. Here, an AIH model of mouse was induced by Concanavalin A (Con A). It found that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in mice with the treatment of OA. Hematoxylin-eosin staining showed that the liver injury was attenuated by OA, and TUNEL staining indicated that the cells apoptosis of liver was weakened in mice with OA treatment. ELISA analysis of cytokines and chemokines suggested that OA reduced the expression of IL-6, IL-17A, CCL2, CXCL1 and CXCL10, but promoted the expression of IL-10 and TGF-β in mice. The mRNA levels of IL-17A in liver and spleen tissues were also significantly decreased, on the contrary, the mRNA levels of IL-10 in liver and spleen tissues were increased. The proportion of Treg/Th17 detected by flow cytometry revealed that OA promoted the differentiation of Treg and inhibited the differentiation of Th17 both in the liver and spleen. The results of this study demonstrated the inhibitory effects of OA on AIH-induced liver injury and the inflammatory response of AIH, and revealed that OA affected the balance of Treg/Th17 and shifted the balance toward Treg differentiation. It provided new potential drugs for the prevention of AIH.
研究领域:
免疫学
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药理学
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肝病学
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
Bochen Song,Peng Li,Shaojia Yan,Yan Liu,Mingkun Gao,Huiyuan Lv,Zengpeng Lv,Yuming Guo
This study aimed to investigate the effects of dietary astragalus polysaccharide (APS) supplementation on the immune function, gut microbiota and metabolism of broiler chickens challenged with necrotic enteritis (NE). Two hundred forty Arbor Acres broiler chicks (one day old) were randomly assigned using a 2 × 2 factorial arrangement into two groups fed different levels of dietary APS (0 or 200 ppm of diet) and two disease challenge groups (control or NE challenged). The results showed that NE infection significantly increased FCR, mortality rate, Th17/Treg (Th17 cells% in blood and ileum, Th17/Treg, IL-17 and IL-17/IL-10 in blood), NO, lysozyme activity and IL-1β in blood, intestinal immune cell proportion and activity (Tc%, Treg% and monocyte phagocytic activity in ileum), intestinal inflammatory cytokines (TLR2, NF-κB, TNF-α and IL- 6) gene expression levels, and the number of Clostridium perfringens in cecum. NE infection significantly reduced body weight gain, thymus index, lymphocyte proliferation activity in blood and ileum, villus height and V/C in jejunum, Th cells% and Mucin2 gene expression in ileum. Dietary APS supplementation significantly increased body weight, feed intake, proportion of immune cells (T cells in blood and Tc, Treg in ileum), lymphocyte proliferation activity, V/C in jejunum, and ZO-1 gene expression in ileum. Dietary APS supplementation significantly reduced FCR and mortality rate, Th17/Treg, Th17%, intestinal pathology scores, intestinal inflammatory cytokine gene expression levels, and the number of Clostridium perfringens in cecum. In addition, broilers challenged with NE significantly increased Staphylococcus and Turicibacte r and reduced α diversity of microbiota in ileum. Dietary APS supplementation significantly increased α diversity, Romboutsia , Halomonas , propionic acid, butyric acid, formononetin, taurine, cholic acid and equol and downregulated uric acid, L-arginine and serotonin in ileum. Spearman’s correlation analysis revealed that Romboutsia, Turicibacter, Staphylocpccus, Halomonas, Streptococcus, Escherichia-Shigella, Prevotella , uric acid, L-arginine, jerivne, sodium cholate and cholic acid were related to inflammation and Th17/Treg balance. In conclusion, APS alleviated intestinal inflammation in broilers challenged with NE probably by regulating intestinal immune, Th17/Treg balance, as well as intestinal microbiota and metabolites.
研究领域:
动物科学
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免疫学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Pathogens
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2021
·Vol. 11
·期 1
·7
·
IF 3.492
Fuchun Zhang,Lingling Sun,Mark K. Lafferty,Joseph B. Margolick,Alfredo Garzino-Demo
CD4+CCR6+T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin,Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.Keywords:CCR6;MIP-3α;immune response;antigen stimulation;Th17
研究领域:
免疫学
·
病毒学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
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IF 3.6
Chen Xiaohui,Lin Shengrong,Liang Yunbang,Xue Xiaomin,Yasen Miersalijiang
Shikonin is a natural product with antioxidant and anti-inflammatory activities. The biological activity of shikonin is still not fully understood, as well as its association with innate immunity and immune and inflammatory bowel disease (IBD) in humans. In this study, the toxicity of shikonin on Raw264.7 cells was assayed by MTT, and polarization of inflammatory macrophages was determined by flow cytometry. The results showed that shikonin can inhibit the polarization of macrophages towards M1 type and significantly inhibited the production of NO in the concentration range of 0.5–1 μM. In addition, after treatment with shikonin, the production of IL-1β and TNF-α was significantly decreased. After shikonin administration, the body weight loss and decrease of colon length were significantly suppressed in DSS-treated colitis C57BL/6 mice. The pro-inflammatory cytokines TNF-α and IL-1β in colonic homogenate were significantly decreased. Shikonin treatment resulted in a notable improvement in the histopathological manifestations in DSS-treated animals at 25/50 mg/kg. Meanwhile, we found that shikonin can regulate differentiation of T helper 17 cell (Th17)/regulatory T cell (Treg), thereby regulating the balance of Th17/Treg cells and exerting an anti-inflammatory effect in IBD animal models. In conclusion, we found that shikonin protects against DSS-induced acute colitis by, among other things, reducing immune cell infiltration, polarizing macrophages, and regulating Th17/Treg differentiation, as well as by downregulating the release of inflammatory cytokines. These findings showed that shikonin can improve inflammation by affecting macrophage polarization. Our experimental data provide experimental evidence and theory basis for research on anti-inflammatory effects for the shikonin as health or functional food. Graphical Abstract
研究领域:
免疫学
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药理学
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消化病学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2026
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IF 14.1
Cheng Zhu,Tiancheng Li,Yu Jin,Yixin Li,Qicheng Liu,Runzhe Fang,Luyao Qu,Xinyue Tang,Ruomei Li,Xiaoyue Zhao,Jin Hao,Bing Fang,Lunguo Xia
Periodontitis is a chronic inflammatory disease characterized by persistent inflammation and limited repair at sites of alveolar bone loss. Although excessive reactive oxygen species (ROS) are recognized drivers of periodontal tissue damage, oxidative stress alone does not fully explain the persistence of inflammation and the failure of regeneration. The immune and metabolic processes that cooperate with oxidative stress in sustaining this disease‐supporting microenvironment remain incompletely defined. In this study, a pronounced T H 17‐skewed CD4 + T cell response is identified in experimental periodontitis, and enrichment of polyamine pathway activation is observed during T H 17 differentiation, suggesting a candidate immunometabolic axis for intervention. Guided by this observation, difluoromethylornithine‐loaded UiO‐66(Ce)‐Mn (DFMO@Ui‐Mn) is developed as a nanozyme platform that integrates the cascade ROS‐scavenging activity of UiO‐66(Ce)‐Mn with DFMO delivery for inhibition of polyamine metabolism. DFMO@Ui‐Mn reduces T H 17 polarization in vitro, alters polyamine‐related metabolic profiles, attenuates inflammatory responses in vivo, lowers the T H 17/Treg ratio, improves osteogenic readouts in a conditioned‐medium model, and promotes alveolar bone repair in ligature‐induced periodontitis. These findings support a therapeutic strategy that combines redox control with immunometabolic intervention to improve the periodontal microenvironment under inflammatory conditions. A pronounced T H 17‐skewed immune response is identified in experimental periodontitis, and enrichment of the polyamine pathway is observed during T H 17 differentiation, suggesting its potential as an immunometabolic target. Inspired by these findings, DFMO@Ui‐Mn is developed as a therapeutic platform combining cascade ROS scavenging with immunometabolic modulation to suppress T H 17 polarization, reduce inflammation, and promote alveolar bone repair in periodontitis.
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PubMed
高影响因子
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