Experimental and Therapeutic Medicine
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2023
·Vol. 25
·期 5
·1-7
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IF 2.7
Zhiguo Wu,Yuchan Wu,Weicheng Zhong,Qingmei Zhong,Shengfang Rao,Dongshan Yu,Xiaolu Luo,Fang Qiu,Zhiying Song,Di Jin,Maoxing Ai,Yu Lan,Gongchang Zhang,Shufeng Song,Baogang Xie,Shuilin Sun
Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)‑induced hepatic fibrosis in Sprague‑Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low‑(aspirin 10 mg/kg + CCl4) and high‑dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL‑1β, transforming growth factor‑β1 (TGF‑β1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4‑induced hepatic fibrosis and liver inflammation. The high‑dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High‑dose aspirin group significantly decreased the levels of pro‑inflammatory cytokines IL‑1β compared with CCl4 group. The high‑dose aspirin group significantly inhibited the expression of TGFβ‑1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4‑induced hepatic fibrosis via inhibition of the TGFβ‑1 pathway and pro‑inflammatory cytokine IL‑1β.
研究领域:
药理学
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肝病学
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炎症
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纤维化
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细胞因子
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
·
IF 5.7
Chong Hou,Fangxu Yin,Dina Xie,Xinyang Zhao,Ruoqing Lin,Songtao Shou
Objective To evaluate the comprehensive protective effects of ulinastatin (UTI) on intestinal structure and function during sepsis and to explore whether UTI restores intestinal motility through mechanisms involving attenuation of interleukin-1β (IL-1β)–mediated inflammation. Methods A murine cecal ligation and puncture (CLP) model was established and mice received intravenous UTI. Primary outcomes included 7-day survival, time to first black stool, fecal output, small-intestinal transit, and blinded histopathology. Barrier integrity was assessed by Alcian Blue–Periodic Acid–Schiff staining for goblet-cell mucin and Claudin-1 immunofluorescence; inflammation by IL-1β, tumor necrosis factor (TNF)-α, and IL-6; and enteric nerve integrity by counting HuD-positive neurons and measuring PGP9.5-labeled nerve fibers. To assess direct effects, primary enteric neurons were stimulated with lipopolysaccharide or IL-1β in vitro . An IL-1β-neutralizing antibody (nAb) was used alone or with UTI to interrogate mechanism. Results UTI improved survival, shortened stool latency, increased pellet output, and enhanced transit after CLP. UTI attenuated intestinal injury, restored goblet-cell mucin production and Claudin-1 expression, and reduced systemic and colonic IL-1β, TNF-α, and IL-6. Moreover, UTI also increased the number of HuD + enteric neurons and preserved PGP9.5-labeled nerve fiber networks. In vitro , UTI preserved βIII-tubulin–defined neuronal morphology and reduced IL-1β secretion. IL-1β nAb reproduced the protective benefits on enteric nerve and intestinal motility; no significant additive benefits were observed when IL-1β nAb was combined with UTI. Conclusion UTI confers broad and integrated protection of the intestine during sepsis. These findings suggest that IL-1β–mediated inflammatory signaling plays a key role in UTI-induced enteric neuroprotection and restoration of intestinal motility.
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JOURNAL OF IMMUNOLOGY
·
2023
·Vol. 210
·期 1
·25-32
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IF 4.4
Han Jing-li,Song Yu-xuan,Yao Wei-juan,Zhou Jing,Du Yiqing,Xu Tao
Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E–deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy–induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E–deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1β in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.
研究领域:
心血管疾病
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免疫学
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内分泌学
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分子生物学
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细胞生物学
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Science China-Life Sciences
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2025
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IF 9.5
Han Ziyi,Fu Jian,Gong Aiyan,Ren Wenkai
The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites, like indole derivatives from tryptophan. However, the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown. Here, we found that bacterial indole-3-propionic acid (IPA) downregulates interleukin-1beta (IL-1β) production in M1 macrophages through inhibition of nuclear factor-kappa B (NF-κB) signaling. Mechanistically, IPA binds specifically with methionine adenosyl-transferase 2A (MAT2A) to promote S-adenosylmethionine (SAM) synthesis, which facilitates the DNA methylation of ubiquitin-specific peptidase 16 (USP16, a deubiquitinase), and in turn promotes Toll-like receptor 4 (TLR4) ubiquitination and NF-κB inhibition. Furthermore, IPA administration attenuates sepsis in mouse models induced by lipopolysaccharides (LPS), showcasing its potential as a microbial-derived adjunct in alleviating inflammation. Collectively, our findings reveal a newly found microbial metabolite-immune system regulatory pathway mediated by IPA.
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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药理学
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Open Medicine
·
2025
·Vol. 20
·期 1
·20251198
·
IF 1.6
Fei Yu,Guangxue Wang,Xingyi Chen,Yanfei Zhang,Cheng Yang,Hui Hu,Liang Wei
We aimed to investigate the protective effect of luteolin against neuron injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R), and to further elucidate the roles of NLRP3 in luteolin-mediated regulation of neuron injury. Using Schwann (SW) 10 cells, an OGD/R-induced neuron injury model was established, and six experimental groups were designated. Subsequently, cell viability and apoptosis were respectively detected by cell counting kit 8 and flow cytometry. Reactive oxygen species (ROS) levels were measured via flow cytometry with a ROS assay kit. Moreover, the expression of interleukin (IL)-6, IL-1β, NLRP3, and MMP9 was examined by real-time quantitative PCR and Western blot. Compared with control cells, OGD/R significantly reduced cell viability and increased apoptosis, ROS levels, and the mRNA levels of IL-6 , IL-1β , NLRP3 , and MMP9 . Luteolin significantly enhanced OGD/R-induced cell viability and alleviated apoptosis in SW10 cells ( P < 0.05). Additionally, luteolin suppressed ROS levels, along with the expression of IL-1β, IL-6, NLRP3, and MMP9 induced by OGD/R. Furthermore, BMS-986299 significantly decreased the cell viability and increased the expression of inflammatory factors in OGD/R-induced SW10 cells treated with luteolin. This inhibitory effect was reversed by NLRP3 knockdown. In conclusion, luteolin may exert a protective effect on OGD/R-induced nerve injury by inhibiting the NLRP3/IL-1β signaling pathway.
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Science Advances
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2025
·Vol. 11
·期 30
·
IF 12.5
Caifeng Deng,Liukang Yu,Xuan Zhao,Yuxiao Chen,Jiabin Mei,Jie Wei,Xiaoyuan Chen,Guanghua Lei,Chao Zeng
Osteoarthritis (OA) is a multifactorial disease characterized by joint inflammation and cartilage degeneration, with no disease-modifying drugs available. The vicious cycle between the inflammatory microenvironment (inflamed soil) and dysfunctional chondrocytes (degeneration-related seeds) drives the chronic progressive deterioration of OA. Here, we report a genetically engineered chondrocyte-mimetic nanoplatform (termed HKL-GECM@MPNPs) comprising a honokiol (HKL)–loaded mitochondrion-targeting nanoparticle core coated with an interleukin-1 receptor type 2 (IL-1R2)–overexpressing chondrocyte membrane. HKL-GECM@MPNPs fuse with OA chondrocytes, transferring IL-1R2 onto the plasma membrane and reprogramming the inflamed microenvironment through IL-1β blockade. Mitochondrion-targeting cores then directly deliver HKL to restore mitochondrial sirtuin-3 in OA chondrocytes, reprogramming the cells’ pathological phenotype. Intra-articular injection of HKL-GECM@MPNPs in OA mice reduces inflammation, alleviates joint pain, and mitigates cartilage damage through a synergistic effect. Moreover, HKL-GECM@MPNPs effectively reverse cartilage degeneration in human OA cartilage explants. This approach highlights the potential of HKL-GECM@MPNPs to combine IL-1β blockade and mitochondrial sirtuin-3 restoration as a promising strategy for OA treatment.
研究领域:
纳米医学
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生物工程
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免疫学
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分子生物学
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药理学
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风湿病学
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Cell Journal
·
2021
·
IF 2.479
Liping Zhou,Haiwei Ye,Lizhen Liu,Yunhua Chen
Objective Human bone marrow mesenchymal stem cell (hBMSC)-derived exosomes exhibit protective effects againstinflammatory diseases. This study aimed to explore the effects of hBMSC-derived exosomes on osteoarthritis (OA) invitro and its related mechanisms. Materials and Methods In this experimental study, we characterised exosomes derived from hBMSCs by transmissionelectron microscopy, nanoparticle tracking and Western blot analysis. Cellular uptake of exosomes was observed byfluorescent microscopy. Cell viability of chondrocytes exposed to interleukin-1 beta (IL-1β) was determined by theCell Counting Kit-8 (CCK-8). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determineexpression levels of genes related to apoptosis, inflammation, cartilage collagen metabolism and mitogen-activatedprotein kinases. Results Fluorescence microscopy revealed that hBMSC-derived exosomes could be taken up by chondrocytes.hBMSC-derived exosomes could significantly enhance cell viability of chondrocytes in response to IL-1β treatment.RT-qPCR showed significant up-regulation of Survivin, Versican, IL-1β, IL-6, NF-κB, MMP-13, MAPK p38, JNK, ERK,Aggrecan and SOX9 expression levels by IL-1β treatment, while their mRNA expression levels decreased after co-culture with exosomes. The anti-inflammatory gene TGF-β was markedly suppressed by IL-1β treatment; however, weobserved its expression after co-culture with exosomes. Additionally, the pro-inflammatory genes IL-1β, IL-6, NF-κB,TNF-α and TNF-β displayed significantly elevated expression levels in the IL-1β group and reduced expression levelsafter co-culture with exosomes. Conclusion hBMSC-derived exosomes may play a protective role in chondrocytes through inhibiting cell apoptosisand the inflammatory response. These results will provide a novel therapeutic strategy for OA.
研究领域:
干细胞生物学
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炎症
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骨科
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分子生物学
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Heliyon
·
2023
·Vol. 9
·期 5
·e15588
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IF 4
Yang Song,Xinyu Xing,Jing Shen,Guo Chen,Li Zhao,Lu Tian,Jie Ying,Yongqiang Yu
Influences of Glycyrrhetinic acid on expression of inflammatory factors in interleukin (IL)-1β-induced SW982 cells and its anti-inflammatory effects were discussed in this study. MTT results showed that Glycyrrhetinic acid (≤80 μmol·L-1) almost has no toxicity on SW982 cells. The results of ELISA and real-time PCR showed that Glycyrrhetinic acid (10, 20 and 40 μmol · L-1) can significantly inhibit the expression of inflammatory factors such as IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1). Western blot analysis showed that Glycyrrhetinic acid remarkably blocked the NF-κB signaling pathway in vitro . Molecule docking showed that Glycyrrhetinic acid could bind to the active site (NLS Polypeptide) of NF-κB p65. Furthermore, observation of rat foot swelling proved that Glycyrrhetinic acid had a significant therapeutic effect on adjuvant-induced arthritis (AIA) in rats in vivo . Collectively, all these findings suggested that Glycyrrhetinic acid might be a promising lead compound worthy of further pursuit as anti-inflammation agent.
研究领域:
药理学
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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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MOLECULAR MEDICINE
·
2026
·Vol. 32
·期 1
·15
·
IF 8.3
Tong Shuai,Zhu Tao,Liang Shuqi,Cui Yuxiao,Ma Yuan,Zhang Xin,Bian Yuhan,Wei Keke,Wu Sha,Ma Jingwei
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by recurrent episodes of mucosal inflammation. During disease progression, macrophages are recruited into the intestinal lamina propria and polarized toward a pro-inflammatory phenotype, where they exacerbate tissue injury by secreting cytokines such as IL-1β, IL-6, and TNF-α. Among these, IL-1β plays a central role, exhibiting both immunomodulatory and pro-inflammatory functions that correlate with disease severity. This study revealed that glycogen metabolism critically regulates IL-1β production and secretion in inflammatory macrophages. Mechanistically, uridine diphosphate-glucose (UDPG), a metabolic intermediate of glycogen metabolism, activates the P2Y 14 receptor, leading to the downstream upregulation of STAT1 expression and enhanced IL-1β production. In parallel, activation of the UDPG–P2Y 14 axis suppresses intracellular cAMP levels, thereby facilitating inflammasome activation and caspase-1 cleavage, ultimately driving IL-1β secretion. Importantly, the glycogen phosphorylase inhibitor ameliorates dextran sulfate sodium induced UC in mice by inhibiting glycogen metabolism. These findings highlight the UDPG–P2Y 14 pathway as a potential therapeutic target for IL-1β-driven inflammatory diseases. Graphical
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JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 6
·1-14
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IF 2.2
Wang Pu,Sun Congcong,Shi Chao,Gao Yong,Luan Chunyu,Yan Chao
Osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes such as articular cartilage degeneration and bone hyperplasia. Mitochondrial dysfunction in chondrocytes has been identified as a critical factor contributing to the progression of OA. Although Evodiamine (Evo) has been demonstrated effeicacy in inhibiting inflammatory responses and matrix degradation in OA chondrocytes, its effects and underlying mechanisms regarding mitochondrial dysfunction in these cells remain to be elucidated. IL-1β was utilized to stimulate chondrocytes in order to establish an in vitro OA model. Subsequently, the proliferation, lactate dehydrogenase (LDH) release, and apoptosis of chondrocytes were systematically evaluated. Mitochondrial function in chondrocytes was evaluated by quantifying of ATP content, ROS level, mitochondrial DNA (mtDNA) copy number, activities of mitochondrial respiratory chain Complexes I and III, as well as mitochondrial membrane potential change. Furthermore, the protein expression levels of the SIRT1/PGC-1α signaling pathway were examined, and an intervention involving the SIRT1 inhibitor EX527 was conducted to elucidate the potential mechanisms underlying the effects of Evo on chondrocytes. Evo treatment significantly elevated the proliferation activity of IL-1β-stimulated chondrocytes, inhibited LDH release and apoptosis, increased mtDNA copy number and ATP content, enhanced the enzymatic activities of Complexes I and III, and suppressed ROS production as well as mitochondrial membrane potential loss. Furthermore, Evo treatment activated the SIRT1/PGC-1α signaling pathway. However, the addition of the SIRT1 inhibitor EX-527 partially attenuated the protective effects of Evo against IL-1β-induced chondrocyte injury by exacerbating mitochondrial dysfunction. Evo promotes mitochondrial biosynthesis, reduces ROS production and improves mitochondrial function by activating SIRT1/PGC-1α pathway, thereby inhibiting IL-1β-induced chondrocyte injury.
研究领域:
药理学
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分子生物学
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细胞生物学
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风湿病学
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线粒体医学
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Discovery Medicine
·
2024
·Vol. 36
·期 181
·266-277
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IF 2
Luo X,Liao H,Peng J,Jiang X
Background Osteoarthritis (OA) is a common disease that causes pain to many older adults. Because the pathogenesis is not fully elucidated, effective drug therapies are currently lacking. This study aimed to determine how salidroside (Sal)-mediated reduction of osteoarthritis development in mice worked and to identify the underlying mechanism. Methods Using in vitro experiments, ATDC5 cells were treated with various concentrations of Sal and interleukin (IL)-1β for 24 hours to mimic OA. An enzyme-linked immunosorbent assay (ELISA) was conducted to detect the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Western blotting was performed to observe the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. In in vivo experiments, pathological examination was used to assess the effects of Sal on alleviating OA progression in mice. Nrf2 signaling and its downstream proteins were further tested by immunofluorescence analysis. Results The results showed that both pro-inflammatory cytokines and ROS were significantly reduced following Sal treatment in a concentration-dependent manner. Western blotting revealed that Sal could inhibit the expression of the NF-κB/hypoxia-inducible factor-2α pathway and activate the Nrf2/heme oxygenase-1 pathway. In vivo experiments showed that the cartilage surface in the saline-treated group eroded to a greater extent than the Sal-treated groups ( p < 0.001). Immunohistochemistry analysis revealed that matrix metallopeptidase (MMP) 9, MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) decreased expression level. In contrast, collagen-II and aggrecan increased in the Sal-treated groups compared to the saline-treated group. Conclusions Our findings indicate that Sal can alleviate OA progression by promoting anti-oxidant expression and inhibiting degradation enzyme expression. These findings suggest that Sal inhibits the NF-κB pathway and its downstream targets through up-regulating the Nrf2 pathway.
研究领域:
医学
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药理学
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PHYTOMEDICINE
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2026
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IF 11.3
Man Wang,Jin-Qing Bai,Jing Cai,Qian-Qian Chen,Xiao-Dong Wen,Lian-Wen Qi,Lei Zhang
Background Cardiorenal syndrome is driven by detrimental heart-kidney crosstalk, where inflammation is a pivotal mediator. However, specific therapies to block this pathological organ communication are still lacking. Salvia miltiorrhiza ( S. miltiorrhiza ) has emerged as a promising multi-target therapeutic candidate, yet its mechanistic role within the cardiorenal network remains largely unexplored. Purpose This study aimed to investigate aqueous extract of S. miltiorrhiza root as a potential treatment for Cardiorenal syndrome by targeting the inflammatory axis between the heart and kidneys. Methods We employed multiple murine models including myocardial infarction, renal ischemia-reperfusion, adenine-induced nephropathy, and a novel dual-injury (myocardial infarction + adenine) model. Cardiac and renal functions were assessed through echocardiography, histological analysis, and serum biomarkers. In vitro studies using neonatal rat cardiomyocytes and renal tubular cells examined the NEU1-TLR4-IL-1β pathway through ChIP-qPCR, co-culture systems, and receptor blockade approaches. Results Aqueous extract of S. miltiorrhiza root demonstrated no direct effect on adenine-induced kidney injury but significantly ameliorated both cardiac and renal damage in the composite cardiorenal injury model, indicating indirect renoprotection via the cardiorenal axis. Mechanistically, salvianolic acid B, the primary active constituent, directly targeted NEU1 in cardiomyocytes, inhibiting NEU1-mediated TLR4 transcription and subsequent IL-1β release. This disruption of IL-1β-mediated cardiorenal cross-talk ultimately protected against kidney injury. Conclusion Salvianolic acid B alleviates kidney injury by suppressing myocardial NEU1 to block pro-inflammatory cross-talk. These findings provide a key mechanistic insight into the cardiorenal protection offered by S. miltiorrhiza .
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