Patients with systemic lupus erythematosus (SLE) have significantly increased cardiovascular risk, and atherosclerosis (AS) is a major cause of long-term mortality. However, whether SLE-specific immune dysregulation drives accelerated AS remains unclear. This study explored the role of interferon-stimulated gene 15 (ISG15) in SLE-associated AS. We first characterized the disease manifestations, then identified disease characteristics at the proteomic and transcriptomic levels via multi-omics analysis of a pristane-induced SLE-ApoE−/− mouse model and integrated analysis of SLE and AS datasets. We found ISG15 was uniquely elevated across atherosclerotic plaque types and correlated with cardiovascular events, with robust interferon-alpha response activation in SLE mice. Further, ISG15 colocalized with CD68⁺ macrophages in plaques, and extended analysis showed it was highly expressed in peripheral blood monocytes of SLE patients. Clinically, ISG15⁺ monocyte proportion was significantly higher in SLE patients with AS, outperforming conventional cardiovascular risk scores and serving as an independent predictor. In conclusion, ISG15 is a critical effector linking SLE immune dysregulation to accelerated AS, and ISG15⁺ monocyte proportion is a promising biomarker for cardiovascular risk stratification in SLE patients.

Atherosclerosis (AS)，a major global cause of cardiovascular mortality，is characterized by significant metabolic reprogramming of plaque macrophages in response to a hostile microenvironment containing cytokines, oxidized lipids, and hypoxia. Macrophage metabolic reprogramming, marked by shifts in glycolysis, fatty acid, and amino acid metabolism has emerged as a critical contributor to chronic inflammatory diseases. This study explores the role of fructose-1,6-bisphosphatase 1 (FBP1) in this process and its functional interplay with hypoxia-inducible factor-1α (HIF-1α). Clinically, FBP1 and HIF-1α levels were significantly elevated in peripheral blood mononuclear cells (PBMCs) and serum from AS patients. ROC analysis indicated their strong potential as diagnostic biomarkers. These findings were corroborated in high-fat diet-fed mice and ox-LDL-stimulated macrophages, which showed increased FBP1 and HIF-1α expression in atherosclerotic lesions and immune cells. FBP1 overexpression mitigated ox-LDL-induced metabolic reprogramming, evidenced by reduced lactate production, reactive oxygen species (ROS) generation, and lipid droplet accumulation. Conversely, FBP1 suppression exacerbated these metabolic alterations. Mechanistically, FBP1 directly interacted with and inhibited the expression of HIF-1α. Inhibition of HIF-1α reverses the exacerbation of cellular metabolic reprogramming induced by FBP1 inhibition. In summary, the results demonstrate FBP1/ HIF-1α axis as mediator of macrophage metabolic reprogramming in AS, highlighting its dual significance as a contributor to disease pathogenesis and a promising basis for clinical diagnosis.

Background: Autophagy exerts a vital role in the development of atherosclerotic lesions. Mounting evidence suggests a significant link between autophagy and atherosclerosis. Methods: Two atherosclerotic plaque datasets were integrated from the Gene Expression Omnibus (GEO) database. After differentially expressed genes (DEGs) were determined, enrichment analyses were subsequently performed on DEGs. We employed weighted gene coexpression network analysis (WGCNA) and cross-linked these modules with DEGs and autophagy-related genes. Subsequently, a prediction model was established for evaluation. RT-PCR was adopted to identify hub gene expression. The consensus clustering analysis on the overlapping genes was executed. Evaluation of immune infiltration was conducted on the merged dataset. A TF-miRNA-mRNA regulatory network was then established for the hub genes. Results: The differential gene expression analysis uncovered 259 DEGs. Enrichment analysis showed that immune and inflammatory reactions were related to atherosclerosis. By intersecting DEGs, WGCNA module genes, and ARGs, 13 overlapping genes were obtained. Four machine learning models identified seven hub genes. Furthermore, six of the seven genes demonstrated potential for disease diagnosis. The prediction model, based on the expression levels of these six genes, yielded satisfactory results. RT-PCR analysis demonstrated that the mRNA expression of six genes meets expectations. Consensus clustering divides 13 overlapping genes into two clusters, C1 and C2, with significant differences in immune infiltration. Immune cell infiltration demonstrated heightened immune activity within the atherosclerotic plaque group. A TF-miRNA-mRNA regulatory network was established for the six genes. Conclusion: It is anticipated that these six genes may serve as significant and valuable targets for future research into atherosclerosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease that significantly increases the risk of cardiovascular diseases, particularly atherosclerosis (AS). Understanding the shared pathogenic mechanisms underlying SLE and AS is crucial for developing effective therapeutic strategies. Macrophages, as pivotal immune cells, play a critical role in the initiation and progression of atherosclerotic plaques within the context of SLE. This review delves into the molecular and cellular mechanisms governing macrophage activation and differentiation in response to SLE-related inflammatory mediators, highlighting their roles in lipid metabolism, plaque stability, and immune regulation. Additionally, we discussed the current treatment modalities for SLE and their impact on macrophage functionality, exploring these effects for atherosclerotic progression. By elucidating the intricate relationship between macrophages, SLE pathophysiology, and AS progression, this review underscores the need for a multidisciplinary approach in managing SLE and its cardiovascular complications, aiming to improve patient survival and quality of life through tailored therapeutic interventions addressing both autoimmune and cardiovascular pathologies.

ObjectiveAtherosclerosis (AS) is the underlying pathology of atherosclerotic cardiovascular disease and a major cause of cardiovascular-related mortality. Chronic inflammation and mitochondrial dysfunction, triggered by the infiltration of various immune cells, are key factors in the progression of AS. However, the interaction and crosstalk between these factors remain unclear.MethodsTwo gene expression datasets, GSE100927 and GSE43292, were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database, covering carotid atherosclerosis and control groups. After identifying the common differentially expressed genes (DEGs), mitochondria-related DEGs (Mito-DEGs) were obtained through Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning approaches. Immune infiltration analysis and comparison were subsequently performed. The single-cell dataset GSE159677 further validated the expression proportions of relevant genes in different cell populations during the progression of AS. Additionally, cell-cell communication and trajectory analysis within the immune landscape were utilized to infer the pathways of cell state transitions within AS clusters. THP-1 cells were cultured in vitro, and the foam cell model was established by the addition of oxidized low-density lipoprotein (ox-LDL). The expression trends of hub Mito-DEGs were confirmed via qRT-PCR.ResultsFrom the GSE100927 and GSE43292 datasets and the MitoCarta3.0 database, three hub Mito-DEGs closely associated with AS were ultimately identified: CASP8, GATM, and LAP3. Subsequent comprehensive bioinformatics analysis of these hub genes further emphasized the importance of the immune system in AS. Immune profiling based on the CIBERSORT algorithm revealed significantly increased infiltration of activated mast cells, monocytes, memory B cells, T follicular helper cells, and M0 macrophages in the immune microenvironment of AS. Single-cell analysis showed that GATM and LAP3 were enriched in monocytes and macrophages, while CASP8 exhibited increased expression in NK cells, T cells, and monocytes. In addition, in vitro cell experiments demonstrated that mRNA expression levels of the hub Mito-DEGs were significantly elevated in the lipid-laden foam cell group compared to the control group, consistent with the expression patterns observed in the single-cell dataset.ConclusionThis study revealed the interaction between Mito-DEGs and the immune system in AS. These findings may provide new insights into therapeutic monitoring and prognosis evaluation.

Background: Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)'s role has been shown to drive immune regulation and inflammation in many human diseases. However, the exact mechanism of action of IFIT1 in AS is unclear, and the specific mechanism of action on METs is also unknown. In this study, we will explore the potential mechanisms of IFIT1 in the formation of METs during AS. Methods: We downloaded GSE100927, GSE193336, GSE159677, IRGs, and METs-related genes for analysis and used qRT-PCR, flow cytometry, and immunofluorescence to detect the expression levels of IFIT1 and METs in plaques from AS patients and mice. The potential association of IFIT1 and METs in macrophages was similarly verified in LPS-induced macrophages. After IFIT1 silencing, the expression levels of METs were detected using qRT-PCR, flow cytometry, immunofluorescence, and WB. In addition, we delved into the potential mechanisms to detect the expression of the STING-TBK1 pathway and explored the interaction between IFIT1 and the STING-TBK1 pathway. Results: Our results showed that IFIT1 was upregulated in AS patients, mouse plaque tissues, and LPS-induced macrophages. The same changes were observed in METs.The decrease in METs after IFIT1 silencing suggests that IFIT1 is involved in the regulation of macrophages through METs. Notably, with the decrease in IFIT1 levels, we observed a corresponding decrease in the STING-TBK1 pathway, which decreased accordingly, suggesting some connection between IFIT1, STING-TBK1, and METs. Validation of the effect of STING-TBK1 on a macrophage basis showed that the STING activator SR-717 increased the expression of METs, while the STING inhibitor H-151 had the opposite result. Interestingly, we added SR-717 and H-151 to si-IFIT1, respectively, and the same changes occurred in METs. Conclusion: In summary, our study suggests that IFIT1 activates METs through the STING-TBK1 pathway, thereby aggravating AS.

Atherosclerosis (AS), the leading cause of cardiovascular diseases, is heavily influenced by inflammation, lipid accumulation, autophagy, and aging. The expression of glycoprotein non-metastatic melanoma B (GPNMB) has been observed to correlate with lipid content, inflammation, and aging, progressively increasing as atherosclerosis advances through its various stages, from baseline to early and advanced phases. However, the interaction between GPNMB and AS is controversial. Knockout of GPNMB has been shown to increase atherosclerotic plaque burden in mice. Conversely, targeted elimination of GPNMB-positive cells reduced atherosclerotic burden. These seemingly contradictory findings underscore the complexity of the issue and highlight the need for further research to reconcile these discrepancies and to elucidate the precise role of GPNMB in the pathogenesis of AS.

BackgroundThere is controversy regarding the relationship between serum iron levels and atherosclerotic cardiovascular disease (ASCVD).ObjectiveTo investigate the relationship between serum iron levels and ASCVD among older adults using data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES).MethodsWe performed a cross-sectional analysis involving 8,682 participants aged 60 years and older, with complete data on serum iron levels and confirmed ASCVD status, sourced from the 2009–2018 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression models were used to examine the association between serum iron levels and ASCVD. To assess the consistency of this association across different demographic groups, subgroup analyses, and interaction tests were performed.ResultsThe group with the highest serum iron levels (fourth quartile, 100–369 μg/dL) exhibited several distinct characteristics: they were the youngest on average (69.57 ± 6.91 years), had the highest proportion of males (61.42%), and the highest hemoglobin levels (14.43 ± 1.33 g/dL). This group also showed the lowest iron supplement usage (19.71 ± 12.85 mg/30 days), white blood cell counts (6.73 ± 2.41 1,000 cells/μL), and serum creatinine levels (0.98 ± 0.45 mg/dL). Moreover, they had higher levels of education and income, a higher likelihood of being married, and a lower body mass index (BMI). Additionally, they had significantly lower rates of diabetes, hypertension, stroke, and heart attacks (all p < 0.05). After adjusting for potential confounders, a linear relationship between serum iron levels and ASCVD was initially observed (OR = 0.97; 95% CI, 0.95–0.99, p < 0.05). However, further analysis using a two-part logistic regression model with an inflection point at 131 μg/dL revealed more nuanced results. For serum iron levels below 131 μg/dL, each 10 μg/dL increase was associated with a 4% decrease in the odds of ASCVD (OR = 0.96; 95% CI, 0.93–0.98, p < 0.001). Conversely, for serum iron levels above 131 μg/dL, each 10 μg/dL increase corresponded to a 1% increase in the odds of ASCVD, though this finding was not statistically significant (OR = 1.01; 95% CI, 0.98–1.08, p > 0.05).ConclusionIn the US elderly population, serum iron levels are negatively associated with ASCVD, particularly when serum iron levels are below 131 μg/dL.

Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which have been widely concerned and explored by re-searchers. Sensitizer is the main factor in determining the therapeutic effect of PDT and SDT. Porphyrins, a group of organic compounds widespread in nature, can be activated by light or ultrasound and produce reactive oxygen species. Therefore, porphyrins as sensitizers in PDT have been widely explored and investigated for many years. Herein, we summarize the classical porphyrin compounds and their applications and mechanisms in PDT and SDT. The application of porphyrin in clinical diagnosis and imaging is also discussed. In conclusion, porphyrins have good application prospects in disease treatment as an important part of PDT or SDT, and in clinical diagnosis and imaging.

Recently, trimethylamine N-oxide (TMAO) has been considered a risk factor for cardiovascular disease and has a proatherogenic effect. Many studies have found that TMAO is involved in plaque oxidative stress and lipid metabolism, but the specific mechanism is still unclear. In our study, meta-analysis and bioinformatic analysis were firstly conducted in the database, and found that the effect of high plasma TMAO levels on promoting atherosclerotic plaque may be related to the expression of key antioxidant genes nuclear factor erytheroid-derived-2-like 2 (NFE2L2/Nrf2) decreased. Next, we assessed the role of Nrf2-mediated signaling pathway in TMAO-treated foam cells. Our results showed that TMAO can inhibit the expression of Nrf2 and its downstream antioxidant response element such as heme oxygenase-1 (HO-1) and glutathione peroxidase4 (GPX4), resulting in increased production of reactive oxygen species and decreased activity of superoxide dismutase, promoting oxidative stress. And TMAO can also promote lipid accumulation in foam cells by inhibiting cholesterol efflux protein expression. In addition, upregulation of Nrf2 expression partially rescues TMAO-induced oxidative stress and reduces ATP-binding cassette A1 (ABCA1)–mediated lipid accumulation. Therefore, TMAO promotes oxidative stress and lipid accumulation in macrophage foam cells through the Nrf2/ABCA1 pathway, which may provide a potential mechanism for the proatherogenic effect of TMAO.

Abstract Macrophages inflammation from variety of risk factors is critical in the rupture of atherosclerotic(AS) plaques. Trimethylamine oxide (TMAO), a dietary metabolite that depends on Gut microbiota, exerts strongly pro-inflammatory effects on Atherosclerosis. Nowadays, mounting research showed that NLRP3 inflammasome activation is essential for the pathogenesis of AS. The present study was to investigate the effect of TMAO on ox-LDL-induced NLRP3 inflammasomes activation of THP-1 cells, and to explore the potential mechanism. Used Cell Counting Kit-8 assay, LDH assay to evaluate the changes of macrophage activity under TMAO and ox-LDL, respectively, to clarify the appropriate dosage. Proteins related to NLRP3 inflammasomes, NF-kb and ERS were determined via Western Blot. Inflammatory cytokine secretion was then examined via ELISA. PCR detected gene levels of inflammatory markers, and caspase-1 activity assay was utilized to detect intracellular caspase-1 activity. The results showed that TMAO could activate NLRP3 inflammasome in ox-LDL-induced THP-1 macrophages and accelerate inflammatory factor release. In addition, TMAO can further activate the expression of ERS-related proteins( including BiP、p-PERK) and NF-KB pathway. NLRP3 inhibitor MCC950, NF-kb inhibitor JSH-23, and ER stress inhibitor 4-PBA reversed TMAO's promoting effect in ox-LDL-induced macrophage. Given these data, we conclude that TMAO promotes NLRP3 inflammasomes activation via the ERS/NF-kb pathway in ox-LDL induced THP-1 macrophages. Reducing the TMAO levels may be a viable approach to prevent atherosclerosis plaque development.

Abstract Background: By associated with inflammation intraplaque, Trimethylamine N-oxide (TMAO) increase the risk of atherosclerotic plaque rupture and has been identified as the independent predictor of cardiovascular events. However, the underlying mechanism is yet unclarity. Accumulating studies have established the critical role of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in mediating intraplaque inflammation and plaque progression. Here, we discussed the role of NLRP3 inflammasome in aggravating ox-LDL-induced macrophage inflammation response to TMAO and its potential mechanism. Results: Our results showed that TMAO enhanced ox-LDL-induced inflammation in THP-1cells. Adding to TMAO remarkably upregulated the expression or mRNA level of NLRP3, Cysteinyl aspartate specific proteinase 1(caspase-1) p20 and Apoptosis associated speck-like protein containing CARD(ASC) and enhanced the activity of caspase-1. An NLRP3 inhibitor (MCC950) reversed the promoting effect of NLRP3 inflammasome activation by TMAO and subsequently macrophage inflammation. Significantly, TMAO also boosted the activation of endoplasmic reticulum stress (ERS) and nuclear factor-kappa B (NF-kB) pathway in ox-LDL-induced cells, manifested as the increasing expression of p-NF-κB, Bip and phosphorylated protein kinase R-like ER kinase (p-PERK). Activation of the NLRP3 inflammasome by TMAO was reversed by the ERS inhibitor 4-PBA or the NF-κB phosphorylation inhibitor JSH-23. Meanwhile, 4-PBA further inhibited the NF-κB phosphorylation and alleviated the NLRP3 inflammasome activation. Conclusions: We concluded that TMAO exacerbates ox-LDL-induced NLRP3 inflammasomes activation and subsequently interleukin (IL)-18 and IL-1b release in THP-1 macrophages, which partly regulated by the activating of the PERK/NF-κB signaling pathway.

OBJECTIVE:To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF)-based routine clinical examinations for post-neurosurgical bacterial meningitis (PNBM) in multicenter post-neurosurgical patients.METHODS:The diagnostic accuracies of routine examinations to distinguish between PNBM and post-neurosurgical aseptic meningitis (PNAM) were evaluated by determining the values of the area under the curve (AUC) of the receiver operating characteristic curve in a retrospective analysis of post-neurosurgical patients in four centers.RESULTS:An algorithm was constructed using the logistic analysis as a classical method to maximize the capacity for differentiating the two classes by integrating the measurements of five variables. The AUC value of this algorithm was 0.907, which was significantly higher than those of individual routine blood/CSF examinations. The predicted value from 70 PNBM patients was greater than the cutoff value, and the diagnostic accuracy rate was 75.3%. The results of 181 patients with PNAM showed that 172 patients could be correctly identified with specificity of 95.3%, while the overall correctness rate of the algorithm was 88.6%.CONCLUSIONS:Routine biomarkers such as CSF/blood glucose ratio (C/B-Glu), CSF lactate (C-Lac), CSF glucose concentration (C-Glu), CSF leukocyte count (C-Leu), and blood glucose concentration (B-Glu) can be used for auxiliary diagnosis of PNBM. The multicenter retrospective research revealed that the combination of the five abovementioned biomarkers can effectively improve the efficacy of the PNBM diagnosis.

BackgroundThe UF‐1000i has been widely used in screening urinary sediments. However, the interference factor of the UF‐1000i in the screening urinary sediments of pregnant women has not been reported. The aim of the study was to demonstrate that epithelial cells (ECs) cause a high false positive rate of white blood cells (WBCs) by the UF‐1000i in pregnant women.MethodsUrine samples were collected from 207 pregnant women. All samples were measured by the UF‐1000i and a microscopic method.ResultsThe areas under the curve (AUC) for WBC and EC counts were 0.837 (95% CI, 0.773–0.901) and 0.844 (95% CI, 0.785–0.903), respectively. The positive rates of the WBC and EC were 73.43% and 37.20%, respectively, by the UF‐1000i, and they were 19.32% and 72.95% by the microscopic method. The positive predictive value, negative predictive value, false positive rates, and false negative rates by the UF‐1000i were for WBC 25.66%, 98.18%, 74.34%, and 1.82%, respectively, and for EC they were 96.1%, 40.77%, 3.9%, and 59.23%, respectively. The coefficient of correlation R value was 0.503 (P < 0.01) between WBC by UF‐1000i and EC by the microscopic method in WBC false positive samples.ConclusionsEC could be an interference factor for the UF‐1000i in screening urinary WBC of pregnant women, and the high false positive rate for WBC may be caused by ECs being misclassified as WBCs by the UF‐1000i. © 2018 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

Macrophage autophagy has a protective role in the development of atherosclerosis; however, it turns dysfunctional in advanced lesions with an increase in p62/sequestosome-1 protein. Little is known about the role and significance of p62 accumulation in atherosclerosis. The present study investigated the association between p62 expression and the process of foam cell formation. Foam cell models were established through incubation of THP-1-derived macrophages with oxidized low-density lipoprotein, and the process of foam cell formation was detected by Oil red O staining. Furthermore, the dynamic change of p62 expression was detected by western blotting and quantitative polymerase chain reaction. Additionally, using gene silencing techniques, the roles of p62 in foam cells were investigated with ELISA, MTT and flow cytometry. The results indicated that besides serving as a marker of autophagy deficiency, the p62 protein could also mediate inflammation and cytotoxicity in advanced foam cells. Additionally, the implication of p62 in autophagy inhibition and foam cell formation makes it a key atherogenic factor under autophagy-deficient conditions.

Objective: Matrix metalloproteinase-9 (MMP-9) plays an important role in the remodeling of the extracellular matrix in atherosclerosis plaques. Autophagy protects macrophages against the processes of vascular disease. Our research explores how autophagy plays roles in macrophages to secret MMP-9.Methods and results: In response to increased doses of oxLDL or CQ we monitored the autophagic flux. Our results revealed that oxLDL was dynamically associated with autophagy and 100 mu g/ml oxLDL blocked autophagic flux in THP-1 cells. Moreover p62/SQSTM1 knocking down and CQ respectively inhibited and increased MMP-9 transcriptional expression. These effects were mediated by inhibition of NF-kappa B.Conclusion: Abundant oxLDL blocked autophagic flux resulting in the aggregation of p62/SQSTM1. Then p62/SQSTM1 was involved in gene expression of MMP-9 via NF-kappa B-dependent signaling, and thus featuring novel plaque vulnerability properties of the atherosclerotic plaque. Understanding the mechanism that selectively modulates p62/SQSTM1 will provide a novel strategy for anti-atherogenesis. (C) 2016 Published by Elsevier Inc.

Objective To study the correlation between urine transferrin (TRF) ,coronary heart disease (CHD) and the degree of coronary artery stenosis .Methods 138 cases of the patients in the hospital were collected because of the coronary disease (CHD group) ,and 108 normal persons were selected as control group (NC group) . The risk factors of cardiovascular diseases were investigated in all groups including sex ,age ,and history of hyperten-sion ,diabetes hypercholesterolemia and smoking .The levels of serum high-density lipoprotein (HDL ) ,low-density lipoprotein(LDL) ,C-reactive protein (CRP) ,creatine kinase-MB(CK-MB) ,Cardiac troponin I(cTnI) and urine trans-ferrin (TRF) were detected .The multiple risk factors of CHD were analyzed by using unconditioned Logistic regres-sion model .Results The contents of LDL ,CRP ,CK-MB ,cTnI and TRF showed significant difference between the two groups (P<0 .01) .The multiple analysis of Logistic regression showed that TRF was an independent risk factor of CHD ,regression coefficient was 0 .729 and relative risk (RR) was 1 .36 (P<0 .01) .The level of TRF was correla-ted to the degree of coronary artery stenosis ,r=0 .886 ,P<0 .01 .Conclusion TRF is an independent risk factor of CHD .The level of TRF would be used to determine the degree of coronary artery stenosis .

Objective To investigate the effects of TLR7 on imiquimod induced apoptosis of THP-1 derived macrophages.Methods Three cell lines ( THP-1 derived macrophages, MDCK cell line and HUVEC cell line) with different capabilities of expressing TLR7 were selected.The survival rates of cells af-ter the treatment with different concentrations of imiquimod were detected by MTT assay.The levels of IL-6 in the supernatants of TLR7 inhibitor chloroquine or TLR7-siRNA treated cells were detected by enzyme-linked immunosorbent assay.The apoptosis of cells was detected by flow cytometry after inhibiting the ex-pression of TLR7.Results Imiquimod induced the apoptosis of THP-1 derived macrophages, MDCK cell lines and HUVEC cell lines.The levels of IL-6 were significantly decreased as the expression of TLR7 was inhibited by treating THP-1 derived macrophages with chloroquine or TLR7-siRNA.Treating THP-1 derived macrophages with chloroquine or TLR7-siRNA did not affect the cell apoptosis induced by imiquimod.Con-clusion Imiquimod could induce the apoptosis of THP-1 derived macrophages through TLR7 independent pathway.

Objective To study the effects of Toll-like receptor 4(TLR4) on oxidized low density lipoprotein ( ox-LDL) induced macrophage apoptosis and its possible mechanism .Methods THP-1 derived macrophages were divided into four groups including untreated control group , ox-LDL treated group , ox-LDL+LPS treated group and tunicamycin treated group .MTT assay and flow cytometry analysis were performed to measure cell vitality and cell apoptosis , respectively .Oil red O staining was used to observe the phagocytosis of lipids by macrophages .The persistent and intense endoplasmic reticulum ( ER) stress markers were de-tected by analyzing the expression of glucose-regulated protein 78 ( GRP78 ) and CCAAT/enhancer-binding protein homologous protein ( CHOP) at mRNA and protein levels by q-RT-PCR and Western blot .Small in-terfering RNA ( siRNA) was used to silence the expression of TLR 4 to further elucidate its possible mecha-nism.Results Flow cytomotry and MTT assay showed that the number of apoptotic cells in ox-LDL+LPS treated group were increased more significantly than that in ox-LDL treated group (P<0.01), and cell apop-tosis in both two groups were greater than that in control group (P<0.01).Compared with control group, the expression of GRP78 and CHOP at mRNA and protein levels were up-regulated in ox-LDL+LPS treated group and ox-LDL treated group (P<0.01), and the expression of GRP78 and CHOP in ox-LDL+LPS treated group was significantly higher than that in ox-LDL treated group (P<0.01).Silenced expression of TLR4 al-leviated the endoplasmic reticulum stress (P<0.05).Conclusion Increased expression of CHOP contribu-ted to cell apoptosis .TLR4 might promote ox-LDL induced macrophage apoptosis through accelerating endo-plasmic reticulum stress .