ANDROLOGIA
·
2022
·Vol. 54
·期 8
·e14455
·
IF 2.532
Cheng Zhang,Jia Chen,Hui Wang,Jing Chen,Mei-Juan Zheng,Xian-Guo Chen,Li Zhang,Chao-Zhao Liang,Chang-Sheng Zhan
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
研究领域:
免疫学
·
泌尿学
·
炎症
·
自身免疫性疾病
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Yishuang Luo,Jinyu Kang,Jia Luo,Zheng Yan,Shengtao Li,Zhuoheng Lu,Yufei Song,Xie Zhang,Julin Yang,Aiming Liu
The development of cholestatic liver injury (CLI) involves inflammation, but the dominant pathway mediating the chemotaxis is not yet established. This work explored key signaling pathway mediating chemotaxis in CLI and the role of Kupffer cells in the inflammatory liver injury. Probe inhibitors T-5224 (100 mg/kg) for AP-1 and C188–9 (100 mg/kg) for STAT3 were used to validate key inflammatory pathways in alpha-naphthylisothiocyanate (ANIT, 100 mg/kg)-induced CLI. Two doses of GdCl 3 (10 mg/kg and 40 mg/kg) were used to delete Kupffer cells and explore their role in CLI. Serum and liver samples were collected for biochemical and mechanism analysis. The liver injury in ANIT-treated mice were significantly increased supported by biochemical and histopathological changes, and neutrophils gathering around the necrotic loci. Inhibitor treatments down-regulated liver injury biomarkers except the level of total bile acid . The chemokine Ccl2 increased by 170-fold and to a less degree Cxcl2 by 45-fold after the ANIT treatment. p-c-Jun and p-STAT3 were activated in the group A but inhibited by the inhibitors in western blot analysis . The immunofluorescence results showed AP-1 not STAT3 responded to inhibitors in ANIT-induced CLI. With or without GdCl 3 , there was no significant difference in liver injury among the CLI groups. In necrotic loci in CLI, CXCL2 colocalized with hepatocyte biomarker Albumin, not with the F4/80 in Kupffer cells. Conclusively, AP-1 played a more critical role in the inflammation cascade than STAT3 in ANIT-induced CLI. Hepatocytes, not the Kupffer cells released chemotactic factors mediating the chemotaxis in CLI.
研究领域:
肝病学
·
免疫学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jia You,Kun Shi,Xi Yang,Huawei Li,Lingnan Zheng,Yuanfeng Wei,JingYi Xu,Yue Li,Zhiyong Qian,Cheng Yi
Malignant pleural effusion (MPE) is a common complication of advanced malignancy with a median survival of less than 5 months. Intrapleural injection is the main treatment for MPE, but there are problems such as the concentration of drugs not being durable and stable in the thoracic cavity, limiting therapeutic efficacy, rapid metabolism of drugs leading to systemic toxicity, a single mechanism of drug. Esculentoside A (EsA) exhibits multi-targeted effects that are potentially valuable to improve the immunosuppressive microenvironment in the thoracic cavity and suppress the development of MPE. But the toxicity and short half-life of EsA severely limit its use. We have developed an EsA delivery system based on a temperature-sensitive hydrogel (PLEL) for local treatment of MPE by intrapleural injection. The EsA/PLEL hydrogel supported slow-release of EsA and maintained a stable intrathoracic drug concentration, which not only significantly inhibited the progression of MPE and prolonged survival, but also reduced the side effects of EsA. We found that downregulating of CXCL1/CXCL2/CXCL3-CXCR2 axis expression to reduce tumour-associated macrophages (TAMs) infiltration and tumour angiogenesis was a potential molecular mechanism for EsA/PLEL hydrogel to control lung cancer MPE. Therefore, this EsA/PLEL hydrogel delivery system has high potential for intrapleural injection therapy of MPE.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Fan Zhan,Xu Yilun,Lu Yafang,Li Xinlin,Xu Mengli,Liu Jinxin,Cai Zhenzhen,Liu Jiayang,Su Jingping,Wang Jialu,Luo Qingming,Zhang Zhihong,Liu Zheng
The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1 GFP/+ Lyz2 RFP/+ mice as bone marrow donors and Krt14 YFP/+ mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.
研究领域:
免疫学
·
皮肤病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2024
·
IF 2.6
Yu Li,Miao Guo,Li Li,Fan Yang,Lidan Xiong
Photoaging, caused by ultraviolet (UV) radiation, is characterized by the senescence of skin cells and reduction of collagens. Although rice fermentation is widely used in the cosmetics, its impact on skin photoaging is still not well understood. Herein, we investigated the possible effectiveness of Maifuyin, a fermented rice product, and its components, succinic acid (SA), and choline, for safeguarding UVA-exposed human dermal fibroblasts (HDFs) against photoaging. In this study, the effects of Maifuyin, SA, and choline on UVA-induced cell death and senescence in fibroblasts were evaluated in cell counting kit-8 (CCK-8), expression of β-galactosidase (β-GAL), and matrix metalloproteinases (MMP)-1. To identify oxidative stress, the investigation focused on reactive oxygen species, glutathione, superoxide dismutase, and malondialdehyde. Additionally, a mRNA sequencing technology (RNA-seq) was applied to study the underlying mechanisms of these components on UVA-induced photoaging. Meanwhile, the level of C–X–C motif chemokine ligand 2 (CXCL2) in the cell supernatant was confirmed to assess the autocrine chemokine level. To reassess the involvement of CXCL2, the expression of β-GAL was evaluated in fibroblasts treated with or without CXCL2. The results indicated that 1 mg/mL Maifuyin and SA inhibited UVA-induced senescence in fibroblasts, MMP-1 expression, and oxidative damage. The RNA-seq revealed 1 mg/mL Maifuyin and SA might be recruited chemokine CXCLs to inhibit MMPs production and fibroblast senescence via TNFα, MAPK, and NF-κB pathways. ELISA results showed a significant reduction of autocrine CXCL2 in UVA-irradiated HDFs by pretreating Maifuyin and SA. The β-GAL staining assay revealed that CXCL2 treatment increased β-GAL activity, while the administration of Maifuyin and SA counteracted this effect in HDFs. These results highlighted the potential use of Maifuyin and SA as promising candidates for anti-photoaging applications.
研究领域:
美容学
·
细胞生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gut Microbes
·
2024
·
IF 12.2
Fangfang Chen,Songhe Guo,Yiqiu Li,Yongfan Lu,Le Liu,Shengxin Chen,Jun An,Ge Zhang
The intracellular bacterium Fusobacterium nucleatum (Fn) mediates tumorigenesis and progression in colorectal cancer (CRC). However, the origin of intratumoral Fn and the role of Fn-infected immunocytes in the tumor microenvironment remain unclear. Here, we observed that Fn-infected neutrophils/macrophages (PMNs/MΦs), especially PMNs, accumulate in tumor tissues and fecal Fn abundance correlates positively with an abundance of blood PD-L1+ PMNs in CRC patients. Moreover, Fn accumulates in tumor tissues of tumor-bearing mice via intragingival infection and intravenous injection. Mechanistically, Fn can survive inside PMNs by reducing intracellular ROS levels and producing H2S. Specifically, the lysozyme inhibitor Fn1792 as a novel virulence factor of Fn suppressed apoptosis of phagocytes by inducing CX3CR1 expression. Furthermore, Fn-driven CX3CR1+PD-L1+ phagocytes transfer intracellular Fn to tumor cells, which recruit PMNs/MΦs through the CXCL2/8-CXCR2 and CCL5/CCR5 axes. Consequently, CX3CR1+PD-L1+ PMNs infiltration promotes CRC metastasis and weakens the efficacy of immunotherapy. Treatment with the doxycycline eradicated intracellular Fn, thereby reducing the CX3CR1+PD-L1+ PMNs populations and slowing Fn-promoted tumor growth and metastasis in mice. These results suggest phagocytes as Fn-presenting cells use mutualistic strategies to home to tumor tissues and induce immunosuppression, and treatment with ROS-enhanced antibiotics can inhibit Fn-positive tumor progression.
研究领域:
肿瘤学
·
免疫学
·
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）