OBJECTIVE: To analyze the differences in the effects of different mechanical stimuli on cells, cytokines, and proteins in synovial fluid of osteoarthritis joints, and to elucidate the indirect mechanism by which mechanical signals remodel the synovial fluid microenvironment through tissue cells. METHODS: Systematically integrate recent literature, focusing on the regulatory effects of different mechanical stimuli on the physicochemical properties of synovial fluid. Analyze the dynamic process by which mechanical stimuli regulate secretory and metabolic activities through tissue cells, thereby altering the physicochemical properties of cytokines and proteins. RESULTS: Appropriate mechanical stimuli activate mechanical signals in chondrocytes, macrophages, and synovial cells, thereby influencing cellular metabolic activities, including inhibiting the release of pro-inflammatory factors and promoting the secretion of anti-inflammatory factors, and regulating the expression of matrix and inflammation-related proteins such as cartilage oligomeric matrix protein, peptidoglycan recognition protein 4, and matrix metalloproteinases. CONCLUSION Mechanical stimuli act on tissue cells, indirectly reshaping the synovial fluid microenvironment through metabolic activities, thereby regulating the pathological process of osteoarthritis.
Humans ; Osteoarthritis/physiopathology* ; Synovial Fluid/chemistry* ; Chondrocytes/metabolism* ; Cytokines/metabolism* ; Macrophages/metabolism* ; Stress, Mechanical ; Cartilage Oligomeric Matrix Protein/metabolism* ; Matrix Metalloproteinases/metabolism* ; Synovial Membrane/cytology*

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans and animals. Chlamydia infection often causes inflammatory response of the body, which seriously affects the health of the host. Cytokines, as key molecules of immune regulation, play an important role in Chlamydia-induced inflammation. Proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6 and interferon γ (IFN-γ), are rapidly activated in the early stage of Chlamydia-induced infection, participating in the recruitment of immune cells to the site of infection and initiating inflammatory response; IL-10 and transforming growth factor β (TGF-β) regulate the activation and function of immune cells in the late stage of inflammation, thus affecting the development of inflammation. There are complex interactions and regulatory mechanisms among cytokines. This review summarizes the role of cytokines in Chlamydia-induced inflammation, and provides an important theoretical basis for the diagnosis and treatment of Chlamydia infection related diseases and the development of vaccines.
Humans ; Cytokines/metabolism* ; Chlamydia Infections/microbiology* ; Animals ; Inflammation/microbiology* ; Chlamydia/immunology*

Objective To study the effect of Mycobacterium tuberculosis (Mtb) Pro-Pro-Glu-59 (PPE59) protein on the biological function of Mycobacterium smegmatis (Ms) and the regulation of host cell immune response. Methods PPE59 gene fragment was obtained by PCR amplification, cloned into pALACE, constructed into recombinant pALACE-PPE59 vector, and electro-transformed into Ms. Western blot was applied to analyse PPE59 expression and subcellular localization. The survival of Ms_Vec and Ms_PPE59 under low acid (pH=3 and pH=5) conditions and active surface pressure sodium dodecyl sulfate (SDS) conditions and their intracellular survival in macrophages were analyzed. ELISA was used to detect the cytokine (IL-1β, IL-6, IL-12, TNF-α and IL-10) expression levels of Ms_Vec and Ms_PPE59 infected macrophages. Results PPE59 protein localized to the cell wall of Ms can enhance the acid-resistance and anti-SDS effect of Ms, which is conducive to the survival of Ms in macrophages. PPE59 significantly decreased the secretion levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α), and promoted the secretion levels of anti-inflammatory cytokine (IL-10). Conclusion PPE59 enhances the survival ability of Ms under low acid and SDS pressure and promotes its intracellular survival by regulating the cytokine secretion levels.
Mycobacterium smegmatis/metabolism* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Bacterial Proteins/metabolism* ; Animals ; Mice ; Antigens, Bacterial/metabolism*

OBJECTIVE: To explore the expression and clinical significance of programmed death receptor 1 (PD-1), Th1, Th2, and Th17 cytokines in multiple myeloma (MM). METHODS: A total of 76 MM patients treated in the Tengzhou Central People's Hospital from May 2021 to May 2023 were collected as MM group, and 48 healthy individuals who underwent physical examination during the same period were included as control group. The expression of PD-1 on the surface of CD4⁺ and CD8⁺ T cells and the levels of serum Th1 cytokines ［interleukin (IL) -2, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α)］, Th2 cytokines (IL-4, IL-6, IL-10) and Th17 cytokines (IL-17) were detected in the two groups. Spearman correlation was used to examine the relationship between PD-1, Th1, Th2 and Th17 cytokines and clinical stage and immune typing of MM patients. Multivariate logistic regression analysis was used to analyze the related factors affecting the efficacy of chemotherapy in MM patients, and the factors were tested for multicollinearity. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of PD-1, Th1, Th2 and Th17 cytokines in chemotherapy efficacy of MM patients. RESULTS: The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in the MM group were higher than those in the control group, while the levels of IL-2, IFN-γ, and TNF-α were lower (all P <0.001). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in R-ISS stage III patients were higher than those in stage II and I patients, and the levels in stage II patients were higher than those in stage I patients (all P <0.05). The IL-2 level in R-ISS stage III patients was lower than that in stage II and I patients, and IL-2 level in R-ISS stage II patients was lower than that in stage I patients (all P <0.05). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in IgG patients were higher than those in IgA, light chain, and non secretory patients, while the level of IL-2 was lower (all P <0.05). Correlation analysis showed that CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 were positively correlated with R-ISS staging in MM patients (r =0.623, 0.635, 0.728, 0.330, 0.742, 0.412), and negatively correlated with immune classification (r =-0.664, -0.756, -0.642, -0.479, -0.613, -0.323). IL-2 was negatively correlated with R-ISS staging in MM patients (r =-0.280), and positively correlated with immune classification (r =0.483). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in the non-remission group were higher than those in the remission group, while the level of IL-2 was lower (all P <0.001). Multivariate logistic regression analysis showed that the increased CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10 and IL-17 were risk factors for the efficacy of chemotherapy in MM patients (OR >1, P <0.05), while the increased IL-2 was a protective factor (OR < 1, P <0.05). The results of multicollinearity test showed that the tolerance of the seven factors included was between 0.714-0.885, and the variance inflation factor was between 1.130-1.400. There was no multicollinearity. The ROC curve analysis results showed that the area under the curve for the combined prediction of chemotherapy efficacy in MM patients by the above 7 factors was 0.942, with specificity of 0.741 and sensitivity of 0.909. CONCLUSION The expression levels of PD-1 on the surface of CD4⁺ and CD8⁺ T cells and serum Th2 and Th17 cytokines in MM patients are high, while Th1 cytokines are low. PD-1, Th1, Th2, and Th17 cytokines are related to clinical stage and immune classification of MM patients. The combined detection of these indicators can help predict the chemotherapy efficacy of MM patients.
Humans ; Programmed Cell Death 1 Receptor/metabolism* ; Multiple Myeloma/blood* ; Cytokines/metabolism* ; Th17 Cells/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism* ; Female ; Male ; Interleukin-10 ; Interferon-gamma ; Middle Aged ; Interleukin-17 ; Interleukin-2 ; Interleukin-4 ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Aged

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*