CELL
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2025
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IF 42.5
Yaozhen Chen,Shouwen Chen,Zhixin Liu,Yafen Wang,Ning An,Yutong Chen,Yihao Peng,Zheng Liu,Qin Liu,Xingbin Hu
The canonical complement-mediated lysis of mature red blood cells (RBCs) leads to severe pathogenesis. However, inhibition strategies targeting complement are not always as efficient as expected, indicating that unknown mechanisms are awaiting elucidation. In this study, we investigate the intracellular events in mature RBCs following complement activation. The collected evidence demonstrates that complement-induced hemolysis is a caspase-8-dependent programmed RBC death. Furthermore, short NLRP3 (miniNLRP3) fragments in RBCs are identified to engage in the assembly of NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC)-caspase-8 complex. Activated caspase-8 directly induces the proteolysis of β-spectrin, thereby disrupting the skeletal network of the RBC membrane, a process we refer to as spectosis. Spectosis signaling is also activated in autoimmune hemolytic anemia or paroxysmal nocturnal hemoglobinuria, and the inhibition of spectosis significantly reduced complement-induced hemolysis. These findings reveal a programmed death cascade in mature RBCs, which may have important implications for the treatment of hemolytic disorders.
研究领域:
免疫学
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血液学
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细胞生物学
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DOI
PubMed
高影响因子
Cell Death Discovery
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2025
·Vol. 11
·期 1
·1-13
·
IF 7
Wei Cheng,Xu Yitian,Zheng Ying,Hong Lizhe,Lyu Chen,Li Haibo,Cao Bin
The mortality associated with influenza A virus (IAV) infection typically results from excessive immune responses, leading to immunopathological lung damage and compromised pulmonary function. Various immunomodulators are seen beneficial when used in conjunction with direct anti-infection treatment. Leukotriene B4 (LTB4) is a derivative of arachidonic acid (AA) and has been shown to be advantageous for numerous infectious diseases, allergies, and autoimmune disorders. Nonetheless, the function of LTB4 in influenza infection remains unclear. This study demonstrates that LTB4 and its primary receptor BLT1, as opposed to the secondary receptor BLT2, act as a protective immune modulator during influenza infection in bone marrow-derived macrophages and mouse models. Mechanistically, LTB4 promotes K27-linked and K48-linked polyubiquitination of the NLRP3 protein at its K886 and K1023 sites via a cAMP/PKA-dependent pathway, which inhibits NLRP3 inflammasome assembly and thereby diminishes subsequent NLRP3 inflammasome activation. The consequent decline in the release of IL-1β and IL-18 leads to a reduction in inflammation caused by viral infection. Furthermore, the administration of a LTB4 treatment in a fatal IAV infection model can mitigate the excessive NLRP3 inflammasome activation and reduce IAV-induced severe pulmonary damage. These findings illustrate the protective function of LTB4 in fatal IAV infection by mitigating the severe inflammation induced by the virus.
研究领域:
免疫学
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病毒学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jiaying Liu,Yuanfan Chen,Jing Zhang,Yun Zheng,Yun An,Chenglai Xia,Yonger Chen,Song Huang,Shaozhen Hou,Dong Deng
Ethnopharmacological relevance The dried fruit of Crataegus pinnatifida Bunge (Hawthorn in Chinese) is a traditional medicine used in China, Japan and Korea for thousands of years. Hawthorn is documented in the Chinese Pharmacopoeia , as a folk medicine that is used to eliminate food, strengthen the stomach, move qi and dissipate blood stasis, treat stagnation of meat and food, gastric distention and fullness, and has anti-inflammatory effects. Vitexin, a flavonoid glycoside, is an important biologically active compound derived from Hawthorn, with significant antioxidant and anti-inflammatory properties. The pharmacological effects of Hawthorn are highly correlated with the antioxidant and anti-inflammatory effects of vitexin. Aim of the study The aim of the present study was to investigate the effect of vitexin on the alleviation of chronic atrophic gastritis (CAG) induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) in a rat model, as well as to elucidate the underlying mechanisms involved. Materials and methods CAG was administered at a concentration of 170 μg/mL MNNG in the drinking water of rats, and the effects of vitexin (30 mg/kg, once daily for 6 weeks) on gastric tissues were subsequently analyzed. Pathological damage was assessed using H&E and AB-PAS staining. Gastrointestinal hormone levels, specifically motilin (MTL) and gastrin (GAS), were quantified using biochemical index determination kits. To evaluate the levels of cytokines, specifically IL-1β and IL-18, in gastric tissue, an enzyme-linked immunosorbent assay (ELISA) was performed. Additionally, to investigate the effects of vitexin on the NLRP3 inflammasome, GES-1 cells were subjected to treatment with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The targeting of NLRP3 by vitexin was assessed in vitro using CESTA, DARTS, and a synthesized biotin-labeled vitexin probe (biotin-vitexin) in conjunction with dual immunofluorescence. RT-PCR, Western blotting and immunofluorescence were used to evaluate the ameliorative effect of oysterin on LPS + ATP-induced GES-1 cells in vitro. Results Administration of vitexin significantly alleviated the symptoms of chronic atrophic gastritis (CAG) by reducing weight loss and minimizing gastric tissue damage. Treatment with vitexin in CAG rats effectively reduces the production of pro-inflammatory cytokines. Furthermore, vitexin attenuated the activation of the NLRP3 inflammasome in CAG induced by MNNG. Mechanistic experiments showed that NLRP3 is a direct cellular target of vitexin, while vitexin inhibited rat NLRP3 inflammasome. Conclusion Vitexin mitigates MNNG-induced CAG, and its protective effect is linked to the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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民族药理学
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胃肠病学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2024
·Vol. 29
·期 6
·1-11
·
IF 3.4
Wenjie Ge,Xian Zhang,Qing Wang,Jianjie Mao,Pengfei Jia,Jianping Cai
Knee osteoarthritis (KOA) is a major cause of disability in elderly individuals. Dicoumarol is a coumarin‑like compound derived from sweet clover [Melilotus officinalis (L.) Pall]. It has been suggested that dicoumarol exhibits various types of pharmacological activities, including anticoagulant, antitumor and antibacterial effects. Due to its various biological activities, dicoumarol has a potential protective effect against OA. Therefore, the present study aimed to assess the effects of dicoumarol on knee osteoarthritis. In the present study, dicoumarol was found to protect rat synoviocytes from lipopolysaccharide (LPS)‑induced cell apoptosis. Western blot analysis showed that dicoumarol significantly reduced the protein expression levels of fibrosis‑related markers and inflammatory cytokines (Tgfb, Timp, Col1a, Il1b and Il18). The inhibitory rates of these proteins were all >50% (P<0.01) compared with those in the LPS and ATP‑induced group. Consistently, the mRNA expression levels of these markers and cytokines were decreased to normal levels by dicoumarol after the treatment of rat synovial fibroblasts with LPS and ATP. Mechanistic studies demonstrated that dicoumarol did not affect NF‑κB signaling, but it did directly interact with NOD‑like receptor protein 3 (NLRP3) to promote its protein degradation, which could be reversed by MG132, but not NH4Cl. The protein half‑life of NLRP3 was accelerated from 26.1 to 4.3 h by dicoumarol. Subsequently, dicoumarol could alleviate KOA in vivo; knee joint diameter was decreased from 11.03 to 9.93 mm. Furthermore, the inflammation and fibrosis of the knee joints were inhibited in rats. In conclusion, the present findings demonstrated that dicoumarol could impede the progression of KOA by inhibiting NLRP3 activation, providing a potential treatment strategy for KOA.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Xiaqing Wu,Huan Chen,Yushan Tian,Hongjuan Wang,Hongwei Hou,Qingyuan Hu,Congyi Wang
Obesity and obesity-related metabolic diseases are causally linked to inflammatory activation. Proinflammatory macrophage infiltration and NLRP3 inflammasome activation contribute to chronic inflammation and insulin resistance. Alleviating inflammatory responses is a reliable method to restore insulin sensitivity and reduce the severity of metabolic syndrome. Solanesol, rich in anti-inflammatory foods (potato, tomato, eggplant, chili peppers), has demonstrated anti-inflammatory properties, but whether it plays a beneficial role in obesity-induced chronic inflammation remains poorly understood. In this study, we investigated the effects of solanesol on the NLRP3 inflammasome and inflammatory responses both in vitro and in high-fat diet (HFD)-fed mice. We found that oral administration of solanesol reduced weight gain, insulin resistance, and inflammation in epididymal white adipose tissue (eWAT) in both HFD-fed obese mice and mice concurrently treated with HFD. This effect was involved with reducing macrophage inflammation and inactivating the NLRP3 inflammasome by reducing K+ efflux and ROS production in macrophages. Solanesol also reprogrammed the phenotype of inflammatory macrophages. Taken together, our study suggests that solanesol may be a promising candidate for treating obesity and obesity-related metabolic diseases.
研究领域:
医学
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免疫学
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代谢研究
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PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Jian Cui,Meng Yang,Chengli Yu,Haidong Zhang,Yuan Gong,Yang Hu,Yue Wang,Qingxin Yuan,An Pan,Jiepin Li,Yaowen Hu,Zecheng Jin,Xuemei Peng,Anyuan Wu,Junwei Wang,Qian Wang,Yinan Zhang,Lihong Hu
Aberrant activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to the pathogenesis of fatal and perplexing pulmonary diseases. Although pharmacological inhibition of the NLRP3 inflammasome brings potent therapeutic effects in clinical trials and preclinical models, the molecular chaperones and transition governing its transformation from an auto-suppressed state to an active oligomer remain controversial. Here, this work shows that sesquiterpene bigelovin inhibited NLRP3 inflammasome activation and downstream pro-inflammatory cytokines release via canonical, noncanonical, and alternative pathways at nanomolar ranges. Chemoproteomic target identification discloses that bigelovin covalently bound to Cys168 of RACK1, disrupting the interaction between RACK1 and NLRP3 monomer and thereby suppressing NLRP3 inflammasome oligomerization in vitro and in vivo. Bigelovin treatment significantly alleviates the severity of NLRP3-related pulmonary disorders in murine models, such as LPS-induced ARDS and silicosis. These results consolidated the intricate role of RACK1 in transiting the NLRP3 state and provided a new anti-inflammatory lead and therapy for NLRP3-driven diseases.
研究领域:
免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
·
IF 4.2
Liu-Gen Cui,Miao-Miao Zhai,Jian-Jian Yin,Zhi-Mo Wang,Shu-Hui Wang,Yue-Jiao Zhou,Pei-Pei Li,Yang Wang,Li Xia,Pei Wang,Xue-Xiang Cha,Li-Rong Zhang,Sheng-Na Han
Several studies have associated the epitranscriptomic RNA modification of N6-methyladenosine (m 6 A) with cardiovascular diseases; however, how m 6 A modification affects cardiomyocyte pyroptosis after myocardial infarction (MI) remains unknown. Here, we showed that AlkB homolog 5 (ALKBH5), an m 6 A demethylase, is crucial in cardiomyocyte pyroptosis after MI. We used MI rat and mouse models, a cell hypoxia model of rat primary cardiomyocytes (RCMs), and rat embryonic ventricle cell line (H9c2) to explore the functional role of m 6 A modification and ALKBH5 in the heart and cardiomyocytes. Using plasmids and small interfering RNAs, the expressions of ALKBH5 and NOD-like receptor family pyrin domain-containing 3 (NLRP3) were determined to study their functions in regulating cardiomyocyte m 6 A and pyroptosis, respectively. We characterized the role of ALKBH5, which exhibited elevated expression in the ischemic heart tissue of rats and mice and hypoxic cardiomyocytes (RCMs and H9c2 cells). ALKBH5 knockdown alleviated hypoxia-induced H9c2 cell pyroptosis by inhibiting NLRP3 inflammasome activation, whereas ALKBH5 overexpression had the opposite effect. NLRP3 knockdown alleviated hypoxia-induced H9c2 cardiomyocyte pyroptosis by inhibiting ALKBH5 expression, whereas NLRP3 overexpression had the opposite effect. Mechanistically, ALKBH5 mediated m 6 A modification of NLRP3 mRNA in an IGF2BP2-dependent manner, and NLRP3, as a nuclear transcription factor, regulated the ALKBH5 transcription process. Targeting the ALKBH5-NLRP3 loop with the small-molecule inhibitors alleviated cardiomyocyte pyroptosis. Our results highlight that ALKBH5-NLRP3 forms a positive feedback loop that promotes cardiomyocyte pyroptosis after MI. Therefore, inhibiting the ALKBH5-NLRP3 loop is a potential strategy for treating cardiovascular diseases.
研究领域:
心血管疾病
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表观转录组学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-13
·
IF 6.1
Li Jing,Wang Xiaochen,Bai Jie,Wei Huangzhao,Wang Wenbo,Wang Shuai
Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.
研究领域:
医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Shuai Zhan,Ningjing Zhang,Yijie Lou,Xia Ding,Zhe Chen,Yun Huang,Wanjing Ding
Acute lung injury (ALI), characterized by uncontrolled inflammatory responses, is a critical condition with limited clinical treatment options. Activation of the NLRP3 inflammasome represents a pivotal event in ALI pathogenesis. Although targeting NLRP3 (The NOD-like receptor (NLR) family member containing a pyrin domain 3) inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the pulmonary inflammation is modulated remains controversial. Here, we demonstrate that 475A, a highly selective ROCK2 (Rho-associated coiled-coil forming protein kinases 2) inhibitor, effectively attenuates pulmonary inflammation and alleviates lung injury. Mechanistically, 475A promotes NLRP3 protein ubiquitination and subsequent proteasomal degradation by disrupting YAP (Yes-associated protein)-NLRP3 protein interactions, thereby suppressing inflammatory cytokine production in macrophages. This study provides the first evidence linking ROCK2 inhibition to enhanced NLRP3 degradation in ALI treatment, paving the way for developing 475A as a therapeutic agent and establishing the ROCK2/YAP/NLRP3 axis as a novel strategy for treating NLRP3-driven inflammatory diseases.
研究领域:
免疫学
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药理学
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分子生物学
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
GeoHealth
·
2024
·Vol. 8
·期 4
·e2023GH000888
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IF 4.3
Xiaoning Wang,Xin Sui,Yangyang Sun,Ziqi Cui,Ning Ma,Shuai Wang,Jun Yang,Fengying Liu,Weijie Yang,Zhenyu Xiao,Tong Zhu,Yuan Luo,Yongan Wang
The Multi-Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod-like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to the cytotoxicity induced by various organophosphorus pesticides (OPPs). The study demonstrated that exposure to six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, and dimethoate) led to significant cytotoxicity in BV2 cells, which was accompanied by increased expression of NLRP3 inflammasome complexes (NLRP3, ASC, Caspase-1) and downstream inflammatory cytokines (IL-1β, IL-18), in which the order of cytotoxicity was dichlorvos > dipterex > dibrom > paraoxon > fenthion > dimethoate, based on the IC 50 values of 274, 410, 551, 585, 2,158, and 1,527,566 μM, respectively. The findings suggest that targeting the NLRP3 inflammasome pathway could be a potential approach for developing broad-spectrum antitoxic drugs to combat multi-OPPs-induced toxicity. Moreover, inhibition of NLRP3 efficiently protected the cells against cytotoxicity induced by these six OPPs, and the expression of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 decreased accordingly. The order of NLRP3 affinity for OPPs was dimethoate > paraoxon > dichlorvos > dibrom > (fenthion and dipterex) based on K D values of 89.8, 325, 1,460, and 2,690 μM, respectively. Furthermore, the common molecular mechanism of NLRP3-OPPs was clarified by the presence of toxicity effector groups (benzene ring, nitrogen/oxygen-containing functional group); =O, -O-, or =S (active) groups; and combination residues (Gly271, Asp272). This finding provided valuable insights into exploring the common mechanisms of multiple threats and developing effective therapeutic strategies to prevent OPPs poisoning. Key Points The NLRP3 inflammasome potentially contributes to cytotoxicity induced by six types of OPPs Inhibition of the NLRP3 pathway effectively prevented cytotoxicity caused by six OPPs The study proposed targets for broad-spectrum antitoxic drugs to prevent OPPs-poisoning Plain Language Summary This study aimed to explore the role of Nod-like receptor 3 (NLRP3) inflammasome activation in organophosphorus pesticide (OPPs)-induced cytotoxicity. Six different OPPs, including dimethoate, paraoxon, dichlorvos, dibrom, fenthion, and dipterex, were introduced to BV2 cells and caused significant cytotoxicity along with increased expression of NLRP3 inflammasome complexes and downstream cytokines. Inversely, inhibition of NLRP3 protected against these OPPs. We believe that our study makes a significant contribution to the literature because it suggests that the NLRP3 inflammasome pathway may be a common mechanism of multi-OPPs-induced cytotoxicity. By introducing a therapeutic target for OPPs poisoning prevention, broad-spectrum antitoxic drugs may be designed to effectively protect against OPPs-induced cytotoxicity.
研究领域:
毒理学
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免疫学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ziliang He,Yeye Hu,Ying Zhang,Jing Xie,Zhiqiang Niu,Guigui Yang,Ji Zhang,Zixuan Zhao,Shuai Wei,Haifeng Wu,Weicheng Hu
Background Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. Purpose This study aimed to explore the protective mechanism of AS in PD. Methods Targets associated with AS and PD were identified from the Swiss Target Prediction, Similarity Ensemble Approach, PharmMapper, and GeneCards database. A protein-protein interaction (PPI) network was constructed to identify potential therapeutic targets. Concurrently, GO and KEGG analyses were performed to predict potential signaling pathways. To validate these mechanisms, the effects of AS on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice were investigated. Furthermore, neuroinflammation and the activation of the NLRP3 inflammasome were assessed to confirm the anti-inflammatory properties of AS. In vitro experiments in BV2 cells were then performed to investigate the mechanisms of AS in PD. Moreover, CETSA, molecular docking, and molecular dynamics simulations (MDs) were performed for further validation. Results Network pharmacology analysis identified 17 potential targets affected by AS in PD. GO and KEGG analyses suggested the biological roles of these targets, demonstrating that AS interacts with 149 pathways in PD. Notably, the NOD-like receptor signaling pathway was identified as a key pathway mediating AS's effect on PD. In vivo studies demonstrated that AS alleviated motor dysfunction and reduced the loss of dopaminergic neurons in MPTP-induced PD mice. In vitro experiments demonstrated that AS substantially decreased IL-1β release in BV2 cells, attributing this to the modulation of the NLRP3 signaling pathway. CETSA and molecular docking studies indicated that AS forms a stable complex with NLRP3. MDs suggested that ARG578 played an important role in the formation of the complex. Conclusion In this study, we first predicted that the potential target and pathway of AS's effect on PD could be NLRP3 protein and NOD-like receptor signaling pathway by network pharmacology analysis. Further, we demonstrated that AS could alleviate symptoms of PD induced by MPTP through its interaction with the NLRP3 protein for the first time by in vivo and in vitro experiments. By binding to NLRP3, AS effectively inhibits the assembly and activation of the inflammasome. These findings suggest that AS is a promising inhibitor for PD driven by NLRP3 overactivation.
研究领域:
神经科学
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药理学
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
·
IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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免疫学
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呼吸医学
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传统中医
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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）