BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway.

BACKGROUND: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms. METHODS: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism. RESULTS: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway. CONCLUSION: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Additional ratios of hydrolysates from lignocellulosic digestate at different hydrothermal temperatures influencing anaerobic digestion performance.

Hydrothermal treatment (HT) is envisaged as a promising technology to treat the lignocellulosic biomass. HT temperature is an important parameter influencing the hydrolysate compositions such as organic compounds and potential inhibitors, and therefore affect the subsequential anaerobic digestion (AD) process. Herein, HT-AD was employed to treat the wheat straw-derived digestate. The HT temperature of 190 °C was proved to be the best performance with a higehst reducing sugar yield (45.05 mg g-1) in the hydrolysate and a highest methane yield (120.8 mL gTS-1) from the AD of the hydrolysate, which was 42.5% higher than the methane yield in the control without the hydrolysate addition (84.8 mL gTS-1). 3-Furaldehyde was the dominant organic in the hydrolysates. The HT temperature of 210 °C led to the presence of AD inhibitory moieties (e.g., phenols and furans) in the hydrolysate, resulting in a low methane yield. Although the treatments with the addition of 100% hydrolysate outperformed those of 50% hydrolysate in the methane yields in the late stage, the latter had higher methane yields in the first stage, suggesting that the additional ratios of hydrolysates should be carefully considered in AD, especially the detrimental effects of inhibitors and adaptability issues of AD consortia. The MiSeq sequencing showed that the hydrolysis/acidogenesis was dominant in the first stage, while methanogenesis became dominant in the late stage with the acetoclastic/hydrogenotrophic methanogens (Methanosarcina and Methanobacterium) enriched in the hydrolysate-feeding reactors. These findings demonstrated that a integration of HT-AD was a promising approach for the digestate valorization and to reduce the potential carbon emission from waste treatments.

Subgingival Microbial Profiles of Young Chinese Adults with Stage I/II Periodontitis, Gingivitis and Periodontal Health Status.

OBJECTIVE: To analyse the subgingival microbiota of Stage I/II periodontitis, gingivitis with different degrees of severity, and periodontal health in subjects in a Chinese young adult population. METHODS: Subgingival plaque samples were collected from 15 Stage I/II periodontitis patients, 38 gingivitis patients and 15 periodontally healthy individuals, all aged from 18 to 21 years. Gingivitis patients were divided into two subgroups according to the Bleeding Index (BI) of their sampled teeth: gingivitis with above median BI (G-HBI) and below median BI (G-LBI). The subgingival plaque samples were collected from teeth 16, 26, 36, 46, 11 and 31 according to FDI notation. The V3-V4 region of the 16S rRNA gene of all the samples was sequenced and analysed. RESULTS: The Stage I/II periodontitis, gingivitis and periodontal health groups showed distinct subgingival microbiota profiles. When the gingivitis patients were stratified into two subgroups, the community structure of G-HBI showed no significant difference from early-stage periodontitis, but differed from G-LBI and the healthy group. Most periodontitis-related taxa were most abundant in Stage I/II periodontitis, followed by G-HBI, G-LBI and the periodontally healthy group. Porphyromonas gingivalis, Filifactor alocis, Tannerella forsythia, Saccharibacteria TM7 G-5 356, Lachnospiraceae G-8 500, Peptostreptococcaceae spp. and Syntrophomonadaceae VIIIG-1 435 were associated with Stage I/II periodontitis. Porphyromonas 275, Leptotrichia 417 and Saccharibacteria TM7 G-2 350 were associated with gingivitis. Porphyromonas gingivalis was significantly more abundant in G-HBI than in G-LBI. CONCLUSION: Within the limitations of this preliminary study, gingivitis and early-stage periodontitis were associated with an increased degree of dysbiosis in the subgingival microbiota in a Chinese young adult population.

Polyglutamine-Specific Gold Nanoparticle Complex Alleviates Mutant Huntingtin-Induced Toxicity.

Huntington's disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs-JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its ß-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs-JLD1, we generated a complex (AuNPs-JLD1-PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs-JLD1-PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.

LOX-1 Regulates P. gingivalis-Induced Monocyte Migration and Adhesion to Human Umbilical Vein Endothelial Cells.

Porphyromonas gingivalis (P. gingivalis) is one of the main periodontal bacteria. This pathogen was reported to enhance monocyte migration and adhesion to endothelial cells in atherosclerosis. The scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a pivotal role in atherogenesis. The aim of this study was to investigate whether LOX-1 modulates P. gingivalis-mediated monocyte migration and adhesion to endothelial cells and how it works. The results showed that the migration and adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) were significantly enhanced when HUVECs or THP-1 cells were challenged with P. gingivalis. Meanwhile, the expression level of LOX-1 in both HUVECs and THP-1 cells were also significantly increased by P. gingivalis stimulation. It is well known that ligand/receptor pairs monocyte chemoattractant protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2), selectins/Integrins, and cell adhesion molecules (CAMs)/Integrins mediate monocyte migration and adhesion to endothelial cells. In this study, LOX-1 was demonstrated to be crucially involved in P. gingivalis-induced THP-1 cell migration and adhesion to HUVECs, by regulating expression of ligands MCP-1, intercellular adhesion molecule-1 (ICAM-1) and E-selectin in HUVECs and that of their receptors CCR2 and Integrin αMß2 in THP-1 cells. The nuclear factor-kappa B (NF-κB) signaling pathway was proved to be involved in this process. In conclusion, LOX-1 plays a crucial role in P. gingivalis-induced monocyte migration and adhesion to endothelial cells. This result implies LOX-1 may act as a bridge in linking periodontitis to atherosclerosis.

Construction of effective receptor for recognition of avian influenza H5N1 protein HA1 by assembly of monohead glycolipids on polydiacetylene vesicle surface.

Fast and sensitive detection of epidemic virus is of the utmost importance for human being in nowadays. Various biosensors have been designed for this goal based on conjugation event between host cell glycolipids and invading virus. However, multihead glycolipids analogous to native receptors on cell surface are known to be very difficult to mimic because of the complexity of chemical synthesis. Here, we developed a new approach where two types of monohead glycolipids, active sialic acid-beta-glucoside (G1) and inactive lactose-beta-glucoside (G2), are embedded onto the surface of a polydiacetylene (PDA) vesicle to mimic native glycolipids on the cell surface. Vesicles prepared in this manner show good selectivity with a 10 ng/mL detection limit and 5 min response time to Hemagglutinin (HA1), which is more sensitive than any HA1 biosensors ever known. Moreover, in the formation of color-changeable vesicles, a very strong synergistic effect between G1 and G2 has been found, offering a novel strategy to construct effective biosensor receptors, as well as a new way to study the surface combination effect that is potentially important to the immunology study of epidemic disease.

Subgingival microbiome in Chinese patients with generalized aggressive periodontitis compared to healthy controls.

OBJECTIVE: The aim of the study was to profile the subgingival microbiome of Chinese adults with generalized aggressive periodontitis (GAgP) using human oral microbe identification microarray (HOMIM), and to compare the results with matched periodontal healthy controls. DESIGN: 15 subjects with GAgP and 15 age- and gender- matched periodontal healthy controls were included. Subgingival plaque samples were collected from the deepest pockets of patients with GAgP and matched sites in controls and then analyzed by 16S rRNA-based microarrays. Student's paired t-test was used to compare clinical parameters and mean number of bacterial taxa detected between the two groups. Fisher's exact probability test and Wilcoxon Rank Sum were used to compare bacterial species between all samples. A multiple linear regression model was used for correlations among age, gender and bacterial with clinical parameters. RESULTS: From a total sum of 379 strains tested, 171 bacterial strains were detected from subgingival plaques of the GAgP patients, more than the 157 strains detected in control group. Mean number of subgingival bacterial taxa detected in GAgP group was 68 (SD = 21.06) while in control group was 45 (SD = 21.60). 47 bacterial taxa were detected more frequently in GAgP group while 12 taxa were more prevalent in control group. The significantly more prevalent and abundant taxa of bacteria in GAgP group included Filifactor alocis, Desulfobulbus sp., Fretibacterium sp., Porphyromonas gingivalis, Tannerella forsythia, Porphyromon as endodontalis, Peptostreptococcaceae spp., Parvimonas micra, Eubacterium nodatum and Eubacterium saphenum. Meanwhile the more abundant taxa in control group were Streptococcus spp. and Pseudomonas aeruginosa. CONCLUSIONS: There are more taxa of bacteria in subgingival plaques of Chinese patients with GAgP than in healthy controls. F. alocis, Desulfobulbus sp., Fretibacterium sp., P. gingivalis and T. forsythia are strongly associated with GAgP. High-throughout microbiological results may help dentists have a better understanding of subgingival microbiome of GAgP.

Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone.

The striking predilection of temporomandibular disorders (TMD) in women, especially during gonad-intact puberty or reproductive years, indicates that oestrogen plays an important role in the progression of TMD, but the underlying mechanism remains unclear. In this study, unilateral anterior crossbite (UAC) was used to create temporomandibular joint osteoarthritis (TMJ OA) models in rats, while 17ß-estradiol (E2) injections were applied to mimic patients with high-physiological levels of oestrogen. Micro-CT scanning, histological staining and real-time PCR assays were preformed to observe the degenerative changes in the mandibular condylar cartilage and subchondral bone. The results showed that obvious degradation was found in the condylar cartilage and subchondral bone of rats with UAC procedure, including decreased cartilage thickness, loss of extracellular matrix, increased apoptotic chondrocytes and expression of pro-inflammatory and catabolic factors, decreased bone mineral density and increased osteoclast activity. E2 supplements aggravated the condylar cartilage degradation but reversed the abnormal bone resorption in the subchondral bone induced by UAC. Our results revealed that high-physiological oestrogen plays a destructive role in condylar cartilage but a protective role in subchondral bone at the early stage of TMJ OA. These dual and distinct effects should be given serious consideration in future OA treatments.

Subgingival Microbiome of Gingivitis in Chinese Undergraduates.

OBJECTIVE: To analyse the microbiome composition of health and gingivitis in Chinese undergraduates with high-throughput sequencing. METHODS: Sequencing of 16S rRNA gene amplicons was performed with the MiSeq system to compare subgingival bacterial communities from 54 subjects with gingivitis and 12 periodontally healthy controls. RESULTS: A total of 1,967,372 sequences representing 14 phyla, 104 genera, and 96 species were detected. Analysis of similarities (Anosim) test and Principal Component Analysis (PCA) showed significantly different community profiles between the health control and the subjects with gingivitis. Alpha-diversity metrics were significantly higher in the subgingival plaque of the subjects with gingivitis compared with that of the healthy control. Overall, the relative abundance of 35 genera and 46 species were significantly different between the two groups, among them 28 genera and 45 species showed higher relative abundance in the subjects with gingivitis, whereas seven genera and one species showed a higher relative abundance in the healthy control. The genera Porphyromonas, Treponema, and Tannerella showed higher relative abundance in the subjects with gingivitis, while the genera Capnocytophaga showed higher proportions in health controls. Porphyromonas gingivalis, Prevotella intermedia and Porphyromonas endodontalis had higher relative abundance in gingivitis. Among them, Porphyromonas gingivalis was most abundant. CONCLUSION: Our results revealed significantly different microbial community composition and structures of subgingival plaque between subjects with gingivitis and healthy controls. Subjects with gingivitis showed greater taxonomic diversity compared with periodontally healthy subjects. The proportion of Porphyromonas, especially Porphyromonas gingivalis, may be associated with gingivitis subjects aged between 18 and 21 years old in China. Adults with gingivitis in this age group may have a higher risk of developing periodontitis.

A novel classification system for the evaluation and reconstruction of oral defects following oncological surgery.

Accurate evaluation of oral tissue defects following oncological surgery is necessary for the subsequent reconstruction. However, there is currently no effective classification system for oral defects in the clinical setting. The present study therefore developed a clinical classification system for the evaluation and reconstruction of oral defects. A retrospective cohort study was performed. A two-dimensional classification system based on coronal computed tomography/magnetic resonance imaging was developed and validated by 145 cases with oral defects. Oral defects could be classified into 6 types (I-VI) horizontally and 2 classes (a and b) vertically. The proportion of the various types was as follows: Type I, 35.9%; type II, 21.4%; type III, 23.4%; type IV, 4.8%; type V, 2.1%; and type VI, 12.4%. Among them, 91 cases (62.8%) were class a and 54 cases (37.2%) were class b. Type Ia-Va represented the unilateral 1-5 subsites involving superficial oral defects without mandibular continuity destruction (88 cases, 60.7%). Type Ib-Vb (+M) represented the unilateral 1-5 subsites involving deep oral defects with segmental mandibular continuity destruction (38 cases, 26.2%). Type I-V (+S) represented the unilateral through and through oral defects with cheek skin involvement (10 cases, 6.9%). Type VI represented bilateral oral defects (18 cases, 12.4%). The present classification system for the evaluation of the oral defects was simple and practical, and could identify the common types of oral defects and guide the reconstruction.

Theoretical determination of the strength of soft noncovalent molecular bonds.

The strength of a simple soft bond under a constant loading rate is studied theoretically. There is a scaling regime where rebinding is negligible and the rupture force scales as const+ [ln (kv) ](2/3) , where kv is the loading rate. The scaling regime is smaller for weaker bonds and broader for stronger bonds. For a loading rate beyond the upper limit of the scaling regime, the bond rupture is deterministic and the thermal effects are negligible. For a loading rate below the lower limit of the scaling regime, the contribution from rebinding becomes important and there is no simple scaling relation between the rupture force and the loading rate. Our theory takes the effect of rebinding in the calculation, therefore we find good agreement between theory and simulation even below the scaling regime.

Accuracy of partial-mouth examination protocols for extent and severity estimates of periodontitis: a study in a Chinese population with chronic periodontitis.

BACKGROUND: Partial-mouth periodontal examination (PMPE) has been widely used in periodontal epidemiologic studies. In this study, the authors evaluate the accuracy of extent and severity estimates from PMPE protocols in a Chinese population. METHODS: The study enrolled 200 individuals with periodontitis, ages 22 to 64 years. Full-mouth examination was performed to determine probing depth (PD), attachment loss (AL), and bleeding on probing (BOP) at mesio-buccal (MB), mid-buccal (B), disto-buccal (DB), mesio-lingual (ML), mid-lingual (L), and disto-lingual (DL) sites per tooth. Extent and severity estimates from 15 PMPE protocols were derived from and compared to full-mouth data. Relative bias (RB) and intraclass correlation coefficients (ICCs) were calculated. Bland-Altman plots were used to evaluate the agreement patterns across disease levels. RESULTS: Of the 15 PMPE protocols, the random half-mouth six-sites per tooth (r6sites) protocol performed best in both extent (AL ≥ 2, ≥ 4, or ≥ 6 mm; PD ≥ 4 or ≥ 6 mm; and BOP) and severity (AL and PD) estimates, with RB within 5.0% and ICCs ≥ 0.950 in most cases. MB-B-DB and MB-B-DL protocols generally resulted in RB within 20.0% for extent and within 5.0% for severity. Protocols involving only interproximal sites (MB-DB, MB-DL, and MB-DB-ML-DL) showed good accuracy in AL (RB within 20.0% for extent and within 3.0% for severity), but overestimated PD (RB 12.5% to 54.2% for extent and >10.0% for severity). The community periodontal index teeth protocol caused severe overestimation of up to 110.4% for extent and 14.6% for severity. CONCLUSION: The r6sites protocol is best for assessing extent and severity for AL, PD, and BOP under the study conditions.

[Accuracy of partial-mouth examination protocols in periodontal epidemiological surveys: a systemic review].

OBJECTIVE: To evaluate the accuracy of partial- mouth periodontal examination (PMPE) protocols frequently used in epidemiological periodontal surveys. METHODS: Articles in English or Chinese published before Jan 31st 2014 were searched, which compared the results of PMPE protocols with those of gold-standard protocol, i.e.full-mouthmesialbuccal-midbuccal-distobuccal-mesiolingual-midlingual-distolingual (MB-B-DB-ML-L-DL) protocol. RESULTS: Twelve articles were included and nine that frequently used PMPE protocols were evaluated. All these protocols underestimated the prevalence scores. For prevalence of probing depth (PD) ≥ 4 mm, 6 mm and attachment loss (AL) ≥ 4 mm, 6 mm, smaller amount of underestimation was observed in community periodontal index of treatment needs (CPITN) teeth (-12.6%--3.5%), full-mouth MB-B-DB (-16.1%--3.5%), full-mouth MB-B-DL (-10.8%--6.1%) and half-mouth MB-B-DB-ML-L-DL (-23.6%--2.0%) protocols. For severity and extent estimates, half-mouth MB-B-DB-ML- L-DL provided lowest biased results (relative bias: -1.0%- 1.1% for severity and -6.7%-0.1% for extent). Full-and half-mouth MB-B-DB also performed well, with relative bias within ± 5.0% in most cases. CPITN overestimated the severity and extent of periodontal disease, the relative bias of which amounted to 42.3% and 38.1%, respectively. CONCLUSIONS: Half-mouth MB-B-DB-ML-L-DL and full-mouth MB-B-DB protocols caused lower biased results in prevalence, severity and extent estimates of PD and AL.

Supercritical CO2 decaffeination of unroasted coffee beans produces melanoidins with distinct NF-κB inhibitory activity.

UNLABELLED: The supercritical CO(2)-decaffeination process causes unroasted coffee beans to turn brown. Therefore, we suspected that the decaffeinated beans contained melanoidins. Decaffeinated unroasted coffee extract absorbed light at 405 nm with a specific extinction coefficient, K(mix 405 nm), of 0.02. Membrane dialysis (molecular weight cut-off, 12 to 14 kDa) increased the K(mix 405 nm) value 15 fold. Gel filtration chromatography showed that the high-MW fraction (MW > 12 kDa) had an elution profile closer to that of melanoidins of medium-roast coffee than to the corresponding fraction of unroasted coffee, indicating the presence of melanoidins in decaffeinated unroasted beans. Using murine myoblast C2C12 cells with a stably transfected nuclear factor-κB (NF-κB) luciferase reporter gene, we found that the high-MW fraction of decaffeinated unroasted beans had an NF-κB inhibitory activity of IC(50) = 499 µg/mL, more potent than that of regular-roast coffee (IC(50) = 766 µg/mL). Our results indicate that melanoidins form during the supercritical CO(2)-decaffeination process and possess biological properties distinct from those formed during the regular roasting process. PRACTICAL APPLICATION: We discovered the roasting effect of decaffeination process, reporting the discovery of melanoidins in green (unroasted) decaf coffee beans. Our results indicated that melanoidins form during the supercritical CO2-decaffeination process and possess biological properties distinct from those formed during the regular roasting process. Our results offer new insights into the formation of bioactive coffee components during coffee decaffeination process.

Immobilization of bioluminescent Escherichia coli cells using natural and artificial fibers treated with polyethyleneimine.

Biosensors based on whole-cell bioluminescence have the potential to become a cost-effective alternative to conventional detection methods upon validation of target selectivity and sensitivity. However, quantitative analysis of bioluminescence is greatly hindered due to lack of control over the total number of cells in a suspending culture. In this study, the effect of surface properties of genetically engineered luminous E. coli cells and fibrous matrices on the immobilization capacity and effectiveness under various environmental conditions were characterized. Four different fibers, including cotton, polyester, viscose rayon, and silk, were investigated. Although cell adhesion was observed on untreated viscose and cotton fibers, viscose fiber pretreated with 0.667% polyethyleneimine (PEI) was found capable of immobilizing the most viable E. coli DPD2234 cells, followed by viscose treated with 0.33% and 1% PEI. The cells immobilized on PEI-treated viscose remained viable and yielded 20% or more bioluminescence signals immediately upon contact with the inducer up to 72 h without feeding nutrients to the cells, suggesting that viscose treated with 0.667% PEI could provide a stable immobilization mechanism for bioluminescent E. coli cells with long sensing period, quick response time, and good signal reproducibility.

Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction.

Angiotensin II (Ang II) produces inflammation and endothelial dysfunction in blood vessels. We tested the hypothesis that interleukin 10 (IL-10), an antiinflammatory cytokine, protects against Ang II-induced vascular dysfunction. Responses of carotid arteries from wild-type and IL-10-deficient mice (IL-10(-/-)) were examined in vitro after overnight incubation with vehicle or Ang II (1 nmol/L). In arteries from wild-type mice, acetylcholine (an endothelium-dependent agonist) produced relaxation that was not affected by Ang II. In contrast, relaxation to acetylcholine in arteries from IL-10(-/-) mice was reduced by >50% by Ang II (P<0.05) and this effect was prevented by a scavenger of superoxide. Vascular superoxide increased approximately 2-fold (P<0.05) after treatment with Ang II in IL-10(-/-) mice but not in wild-type. After systemic administration of Ang II (1.4 mg/kg per day for 10 days), Ang II produced modest impairment of endothelial function in wild-type mice but marked impairment in IL-10(-/-) mice (P<0.05) that was reversed by a superoxide scavenger. Increases in arterial pressure in response to Ang II were similar in wild-type and IL-10(-/-) mice. These findings provide the first evidence that endogenous IL-10 limits Ang II-mediated oxidative stress and vascular dysfunction both in vitro and in vivo suggesting that at least some of the protective effects of IL-10 may occur within the vessel wall.