蜂胶黄酮对大鼠脑缺血再灌注损伤后IL-1β、IL-6和TNF-α含量的影响

目的探讨蜂胶黄酮对脑缺血再灌注损伤的保护作用。方法采用大鼠大脑中动脉栓塞模型（MCAO）,研究蜂胶黄酮对脑缺血再灌注脑梗死体积和行为学评分的影响,对脑组织内IL-1β、IL-6和TNF-α含量的影响。结果蜂胶黄酮能够减少MCAO脑梗死体积和行为学评分,降低脑组织中IL-1β、IL-6和TNF-α的含量（P〈0．05）。结论蜂胶黄酮对大鼠脑缺血再灌注损伤有一定保护作用,其作用机制与降低脑组织中IL-1β、IL-6和TNF-α含量有关。     

Peritoneal cytokines as early markers of peritonitis following surgery for colorectal carcinoma: a prospective study

This study was to investigate if measurement of peritoneal cytokines is valuable for an early diagnosis of peritonitis following colorectal surgery. One hundred consecutive patients who were to undergo elective resection for carcinoma of the sigmoid colon or the rectum were investigated. Abdominal exudate was obtained from a drainage tube daily after surgery for measuring interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. The relationship between peritoneal cytokine levels during the first 3 days after surgery and the development of peritonitis was investigated. Eight patients developed postoperative peritonitis due to anastomotic leakage and pelvic abscess, which was diagnosed on postoperative days 5-8. Peritoneal cytokine levels on postoperative days 1 and 2 were not significantly different between the 8 patients who developed peritonitis and 92 patients who did not: day 1, IL-1βP=0.32, IL-6 P=0.45, TNF-αP=0.85; day 2, IL-1βP=0.26, IL-6 P=0.68, TNF-αP=0.22. In contrast, the cytokine levels on day 3 were significantly higher in patients who developed peritonitis as compared with patients who did not: IL-1βP=0.008, IL-6 P<0.0001, TNF-αP=0.0001. The cytokines significantly increased during the first 3 days in patients who developed peritonitis: IL-1βP=0.049, IL-6 P=0.03, TNF-αP=0.01, while significantly decreased in patients who did not: IL-1βP<0.0001, IL-6 P<0.0001, TNF-αP<0.0001. The outcomes of this investigation showed that the rise in peritoneal IL-1β, IL-6 and TNF-α levels may be an additional early diagnostic predictor of intraabdominal complications following colorectal surgery.     

Repetitive transcranial photobiomodulation but not long-term omega-3 intake reduces epileptiform discharges in rats with stroke-induced epilepsy

Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.     

Ammonia Attenuates LPS-Induced Upregulation of Pro-Inflammatory Cytokine mRNA in Co-Cultured Astrocytes and Microglia

Hepatic encephalopathy (HE) is associated with cerebral microglia activation. Ammonia, a major toxin of HE, activates microglia in vitro but does not trigger pro-inflammatory cytokine synthesis. In the present study we analysed effects of ammonia on lipopolysaccharide (LPS)-induced upregulation of microglia activation and cytokine mRNA as well as on cytokine secretion in mono-cultured microglia and co-cultured astrocytes and microglia. In mono-cultured microglia LPS (100 ng/ml, 18 h) strongly elevated mRNA levels of the microglia activation marker CD14 and the pro-inflammatory cytokines IL-1α/β, IL-6 and TNF-α. NH₄Cl (5 mmol/l) had no effect on LPS-induced upregulation of CD14, IL-1α/β and IL-6 mRNA but enhanced LPS-induced upregulation of TNF-α mRNA in mono-cultured microglia. In co-cultured astrocytes and microglia, however, LPS-induced upregulation of IL-1α/β, TNF-α, IL-6, CD14 but not of IL-10, IL-12A/B or TGFβ_1?3 mRNA was attenuated by NH₄Cl. LPS-induced upregulation of IL-1α/β, IL-6 and TNF-α was also diminished by the TGR5-ligands allopregnanolone and taurolithocholic acid in mono-cultured microglia. NH₄Cl also attenuated LPS-induced release of MCP-1, IL-6 and IL-10 in mono-cultured microglia. mRNA level of surrogate marker for microglia activation (CD14) and for the anti-inflammatory M2-type microglia (CD163, CXCL1, CXCL2) were also elevated in post mortem brain tissue taken from the fusiforme gyrus of patients with liver cirrhosis and HE. The findings suggest that ammonia attenuates LPS-induced microglia reactivity in an astrocyte-dependent way. One may speculate that these anti-inflammatory effects of ammonia may be triggered by neurosteroids derived from astrocytes and may account for absence of microglia reactivity in cerebral cortex of cirrhotic patients with HE.     

IL-12Rβ2 is essential for the development of experimental cerebral malaria

A Th1 response is required for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The role of pro-Th1 IL-12 in malaria is complex and controversial. In this study, we addressed the role of IL-12Rβ2 in ECM development. C57BL/6 mice deficient for IL-12Rβ2, IL-12p40, or IL-12p35 were analyzed for ECM development after blood-stage PbA infection in terms of ischemia and blood flow by noninvasive magnetic resonance imaging and angiography, T cell recruitment, and gene expression. Without IL-12Rβ2, no neurologic sign of ECM developed upon PbA infection. Although wild-type mice developed distinct brain microvascular pathology, ECM-resistant, IL-12Rβ2-deficient mice showed unaltered cerebral microcirculation and the absence of ischemia after PbA infection. In contrast, mice deficient for IL-12p40 or IL-12p35 were sensitive to ECM development. The resistance of IL-12Rβ2-deficient mice to ECM correlated with reduced recruitment of activated T cells and impaired overexpression of lymphotoxin-α, TNF-α, and IFN-γ in the brain after PbA infection. Therefore, IL-12Rβ2 signaling is essential for ECM development but independent from IL-12p40 and IL-12p35. We document a novel link between IL-12Rβ2 and lymphotoxin-α, TNF-α, and IFN-γ expression, key cytokines for ECM pathogenesis.     

血清细胞因子与脑卒中后失眠的相关性研究

目的 探讨血清细胞因子与脑卒中后失眠的相关性。方法 选取我院2014年11月—2015年12月收治的70例脑卒中后失眠且中医辨证为心脾两虚型患者（观察组）,同时选取同期脑卒中后非失眠患者70例（对照组）。比较两组患者血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平,并比较不同程度失眠患者血清TNF-α、IL-6、IL-1β水平。结果 观察组PSQI总评分（13.10±3.45）显著高于对照组的（4.23±2.35）（t=17.90,P<0.05）。观察组患者IL-6、IL-1β水平均显著高于对照组,TNF-α显著低于对照组,差异具有统计学意义（t=38.56,13.61,14.35,均P<0.05）。不同程度睡眠障碍患者TNF-α、IL-6、IL-1β水平比较,差异具有统计学意义（F=8.47,10.36,11.27,均P<0.05）,且随着睡眠障碍程度的增加,IL-6、IL-1β水平呈上升趋势,TNF-α水平呈下降的趋势。进一步相关性分析结果显示睡眠障碍程度与血清TNF-α水平呈负相关,r=-1.856（P<0.05）;IL-6、IL-1β水平呈正相关,r=0.720,0.745（均P<0.05）。结论 细胞因子TNF-α、IL-6、IL-1β与卒中后失眠有显著相关性,在临床工作中对有上述血清细胞因子异常的脑卒中患者给予必要的干预有重要的临床意义。     

Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women

Abstract

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β₁) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O₂?) and hydrogen peroxide (H₂O₂) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O₂₂, H₂O₂ and TNF-α, and lower levels of IL-10 and TGF-β₁ than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O₂? and H₂O₂ release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.     

Baicalein inhibits IL-1β- and TNF-α-induced inflammatory cytokine production from human mast cells via regulation of the NF-κB pathway

Background

Human mast cells are multifunctional cells capable of a wide variety of inflammatory responses. Baicalein (BAI), isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have anti-inflammatory effects. We examined its effects and mechanisms on the expression of inflammatory cytokines in an IL-1β- and TNF-α-activated human mast cell line, HMC-1.

Methods

HMC-1 cells were stimulated either with IL-1β (10 ng/ml) or TNF-α (100 U/ml) in the presence or absence of BAI. We assessed the expression of IL-6, IL-8, and MCP-1 by ELISA and RT-PCR, NF-κB activation by electrophoretic mobility shift assay (EMSA), and IκBα activation by Western blot.

Results

BAI (1.8 to 30 μM) significantly inhibited production of IL-6, IL-8, and MCP-1 in a dose-dependent manner in IL-1β-activated HMC-1. BAI (30 μM) also significantly inhibited production of IL-6, IL-8, and MCP-1 in TNF-α-activated HMC-1. Inhibitory effects appear to involve the NF-κB pathway. BAI inhibited NF-κB activation in IL-1β- and TNF-α-activated HMC-1. Furthermore, BAI increased cytoplasmic IκBα proteins in IL-1β- and TNF-α-activated HMC-1.

Conclusion

Our results showed that BAI inhibited the production of inflammatory cytokines through inhibition of NF-κB activation and IκBα phosphorylation and degradation in human mast cells. This inhibitory effect of BAI on the expression of inflammatory cytokines suggests its usefulness in the development of novel anti-inflammatory therapies.     

Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice

Ischemic stroke is a major cause of morbidity and mortality, yet lacks effective neuroprotective treatments. The aim of this work was to investigate whether treatment with isorhamnetin protected the brain against ischemic injury in mice. Experimental stroke mice underwent the filament model of middle cerebral artery occlusion with reperfusion. Treatment with isorhamnetin or vehicle was initiated immediately at the onset of reperfusion. It was found that treatment of experimental stroke mice with isorhamnetin reduced infarct volume and caspase-3 activity (a biomarker of apoptosis), and improved neurological function recovery. Treatment of experimental stroke mice with isorhamnetin attenuated cerebral edema, improved blood–brain barrier function, and upregulated gene expression of tight junction proteins including occludin, ZO-1, and claudin-5. Treatment of experimental stroke mice with isorhamnetin activated Nrf2/HO-1, suppressed iNOS/NO, and led to reduced formation of MDA and 3-NT in ipsilateral cortex. In addition, treatment of experimental stroke mice with isorhamnetin suppressed activity of MPO (a biomarker of neutrophil infiltration) and reduced protein levels of IL-1β, IL-6, and TNF-α in ipsilateral cortex. Furthermore, it was found that treatment of experimental stroke mice with isorhamnetin reduced mRNA and protein expression of NMDA receptor subunit NR1 in ipsilateral cortex. In conclusion, treatment with isorhamnetin protected the brain against ischemic injury in mice. Isorhamnetin could thus be envisaged as a countermeasure for ischemic stroke but remains to be tested in humans.     

Protective effect of xanthohumol against age-related brain damage

It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg⁻¹ day⁻¹ or 5 mg kg⁻¹ day⁻¹ xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg⁻¹ day⁻¹ xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging.     

Contribution of interleukin-1 receptor accessory protein B to interleukin-1 actions in neuronal cells

Interleukin (IL)-1 is an important neuroimmunomodulator and a key mediator of inflammation during brain disorders. It acts on neuronal and glial cells via binding to the IL-1 type 1 receptor and IL-1 receptor accessory protein (IL-1RAcP). More recently, a neuronal-specific isoform of IL-1RAcP, named IL-1RAcPb, has been identified. Our aim was to determine the role of IL-1RAcPb in IL-1 actions in neuronal and glial cells, and to further explore the signaling mechanisms of IL-1 in neurons. We found that IL-1RAcPb deletion had no effect on IL-1α- and IL-1β-induced activation of the extracellular signal-regulated kinase 1/2 or IL-6 release in glial cultures, although IL-6 release in response to high IL-1α concentration (30 IU/ml) was significantly reduced. We identified the p38 kinase as a key signaling element in IL-1α- and IL-1β-induced IL-6 synthesis and release in neuronal cultures. IL-1RAcPb deletion had no effect on IL-1α- and IL-1β-induced IL-6 release in neurons, but significantly reduced IL-1α- but not IL-1β-induced p38 phosphorylation. Our data demonstrate that the p38 signaling pathway plays an important role in IL-1 actions in neurons, and that IL-1RAcP may regulate some, but not all, neuronal activities in response to IL-1α.     

复合应激型ED大鼠模型促炎细胞因子IL-6、TNF-α和TGF-β1水平的研究

目的:探讨环境雌激素样饲料联合冷刺激诱导的ED大鼠血清与阴茎组织中促炎因子IL-6、TNF-α和TGF-β1的变化及其对ED大鼠阴茎组织纤维化的影响.方法:取100只SD雄性大鼠,20只为正常组(N),其余120只为建模组,以环境雌激素样饲料联合冷刺激予以复合干预,24周后通过APO阴茎勃起实验和交配实验筛选ED大鼠,...     

连翘酯苷对拟AD复合动物模型小鼠学习记忆的改善作用及其机制研究

目的以β淀粉样蛋白损伤自然衰老小鼠建立一种新的复合式老年痴呆(AD)小鼠模型,观察连翘酯苷对复合模型学习记忆障碍的改善作用,并对其机制进行初步探讨。方法采用14月龄C57BL/6小鼠侧脑室注射Aβ25-35形成拟AD复合模型;Morris水迷宫实验观察小鼠学习记忆能力,实验结束取小鼠脑组织用放射免疫分析法检测TNF-α及IL-1的含量;Western blot方法检测GFAP蛋白表达,化学比色法测定ChAT、AchE、SOD酶活性及MDA的含量。结果水迷宫实验中连翘酯苷组可显著改善小鼠的学习记忆能力(P<0.05)。作用机制研究发现:连翘酯苷能降低TNF-α、IL-1的含量(P<0.05),抑制GFAP蛋白表达。提高ChAT、SOD酶活力,降低AchE活性及MDA的含量(P<0.05,P<0.01)。结论连翘酯苷对拟AD复合动物模型学习记忆的改善作用可能与抑制脑内炎症反应,调节胆碱能系统,抗氧化作用等有关。     

Fragile X mental retardation protein-regulated proinflammatory cytokine expression in the spinal cord contributes to the pathogenesis of inflammatory pain induced by complete Freund's adjuvant

Studies have verified that Fragile X mental retardation protein (FMRP), an RNA-binding protein, plays a potential role in the pathogenesis of formalin- and (RS)-3,5-dihydroxyphenylglycine-induced abnormal pain sensations. However, the role of FMRP in inflammatory pain has not been reported. Here, we showed an increase in FMRP expression in the spinal dorsal horn (SDH) in a rat model of inflammatory pain induced by complete Freund's adjuvant (CFA). Double immunofluorescence staining revealed that FMRP was mainly expressed in spinal neurons and colocalized with proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)]. After consecutive intrathecal injection of fragile X mental retardation 1 small interfering RNA for 3 days post-CFA injection, FMRP expression in the SDH was reduced, and CFA-induced hyperalgesia was decreased. In addition, the CFA-induced increase in spinal TNF-α and IL-6 production was significantly suppressed by intrathecal administration of fragile X mental retardation 1 small interfering RNA. Together, these results suggest that FMRP regulates TNF-α and IL-6 levels in the SDH and plays an important role in inflammatory pain.

     

H9N2亚型猪流感病毒诱导小鼠急性肺损伤中TNF-α、IL-1β、IL-6和IL-10的变化和作用

目的探讨H9N2亚型猪流感病毒诱导小鼠急性肺损伤过程中炎症因子的变化和作用。方法通过滴鼻的方法将H9N2亚型猪流感病毒感染BALB/c小鼠,于感染后2、4、6、10、14 d取小鼠肺组织匀浆,分别测定肺组织匀浆中TNF-α、IL-1β、IL-6和IL-10的浓度。结果实验组肺组织匀浆中TNF-α、IL-1β、IL-6和IL-10在不同时间点浓度均显著高于正常对照组(P<0.05),TNF-α和IL-1β于14 d后趋于正常,而IL-6和IL-10增高持续至14d后。结论 H9N2猪流感病毒诱导小鼠急性肺损伤过程中炎症因子发挥重大作用,TNF-α和IL-1β起致炎作用,IL-6可能和IL-10一样,发挥抗炎作用。     

Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-α, IL-6, IL-1β, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-κB activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer’s disease.     

A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia

Inflammation may play a major role in the pathogenesis of preeclampsia (PE). In this meta-analysis, we determined whether maternal polymorphisms and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were associated with PE. All studies investigating the associations between PE and maternal polymorphisms of TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G or serum concentrations of TNF-α, IL-6, and IL-10 were reviewed. We found that neither maternal TNF-α-308G/A (p=0.86, odds ratio [OR]=0.98, 95% confidence interval [CI], 0.76-1.25), IL-6 174G/C (p=0.14, OR=1.23, 95% CI, 0.93-1.61), nor IL-10-1082A/G (p=0.72, OR=1.07, 95% CI, 0.75-1.52) were associated with PE. On the other hand, maternal TNF-α (p<0.00001, weighted mean difference [WMD]=19.63 pg/ml, 95% CI, 18.54-20.72 pg/ml), IL-6 (p<0.00001, WMD=6.58 pg/ml, 95% CI, 5.49-7.67 pg/ml), and IL-10 (p=0.0005, WMD=19.30 pg/ml, 95% CI, 8.42-30.17 pg/ml) concentrations were significantly higher in PE patients versus controls. Our findings strengthen the clinical evidence that PE is accompanied by exaggerated inflammatory responses, but do not support TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G as candidate susceptibility loci in PE.     

间充质干细胞外泌体对海马星形胶质细胞活化的抑制作用研究

目的 探讨间充质干细胞外泌体(MSC-Exo)对海马星形胶质细胞活化的抑制作用.方法 实验通过超速离心法提取脐带MSC-Exo,并使用PKH-26染料标记;MSC-Exo预处理原代海马星形胶质细胞后使用脂多糖(LPS)诱导细胞活化,并分为对照组、LPS组和LPS+MSC-Exo组,进而行免疫细胞化学检测胶质纤维酸性蛋白...