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The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. 催乳素在雄性大鼠瘦素分泌昼夜节律中的可能作用。
C. Mastronardi, A. Walczewska, W. H. Yu, S. Karanth, A. Parlow, S. Mccann
In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 microg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a dopamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 microg), but not IGF-2 (10 microg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0. 1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans.
人体血浆中瘦素浓度有昼夜节律,清晨最低,午夜最高。通过在24小时内每3小时采集一次成年雄性大鼠的血液样本,我们确定大鼠的血浆瘦素浓度也存在昼夜节律,在0130h达到峰值,在0730h达到最低。为了确定这种节律是否受夜间释放的激素控制,我们评估了人类在夜间释放的激素的影响,其中一些激素在夜间也会在老鼠身上释放。在人类中,泌乳素(PRL)、生长激素(GH)和褪黑激素在夜间被释放,促肾上腺皮质激素(ACTH)的释放被抑制。在这些实验中,清醒的大鼠在取出第一个血样(0.3 ml)后立即静脉注射0.5 ml稀释剂或待评估物质,此后每10分钟再抽取0.3 ml血样,持续2小时。高纯度绵羊PRL(500微克)的注射使血浆瘦素迅速增加,并在实验期间持续增加。较低剂量无效。为了确定阻断PRL分泌对瘦素分泌的影响,注射可快速抑制PRL释放的多巴胺-2受体激动剂α -溴代隐碱(1.5 mg)。在10分钟内使血浆瘦素迅速下降,并持续下降120分钟。生长激素降低血浆瘦素的最小有效剂量为1 mg/大鼠。胰岛素样生长因子(IGF-1)(10微克),而不是IGF-2(10微克),也显著降低血浆瘦素。褪黑素是人类和大鼠在夜间释放的,在白天(1100小时)或夜间(2300小时)注射剂量为1mg /大鼠。它没有显著改变瘦素的释放。地塞米松(Dexamethasone, DEX)是一种强效糖皮质激素,在0时无效。1毫克剂量,但产生延迟,显著增加瘦素,表现在注射1毫克剂量后100-120分钟。由于人体内的糖皮质激素在夜间会减少,而此时正是血中瘦素浓度最高的时候,因此我们假设,相对高剂量的DEX导致的瘦素增加可能与大鼠应激后皮质酮释放的反应类似,而糖皮质激素并不是导致瘦素浓度昼夜节律的原因。因此,我们得出结论,夜间PRL分泌的增加可能是夜间瘦素浓度升高的原因,至少部分原因是在大鼠和人类中观察到的。
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引用次数: 34
The effect of a special herbal tea on obesity and anovulation in androgen-sterilized rats. 一种特殊凉茶对雄激素绝育大鼠肥胖和无排卵的影响。
F. Sun, J. Yu
A special herbal tea has been used to treat clomiphene-resistant anovulatory disease and obesity effectively, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of the herbal tea on obesity and anovulation was investigated in androgen-sterilized rats (ASR). The ASR model was established by subcutaneous injection of 1.25 mg testosterone propionate to Sprague-Dawley female rats at the age of 9 days. Rats were sacrificed around 112 days of age. ASR manifested with PCO, anovulation, high food intake, elevated body weight, and obesity. Immunocytochemistry demonstrated that estrogen receptors (ER) were predominantly distributed in the cytoplasm of neuropeptide Y (NPY)-containing neurons in the preoptic area (POA), and the coexpression was also found in the nuclei and fibers of NPY-synthesizing neurons in the arcuate nucleus (ARC). Compared with that in normal control rats, NPY expression was increased, the numbers of ER in hypothalamic ARC-median eminence (ME) decreased, gonadotropin-releasing hormone (GnRH) levels in ME was decreased, serum estrogen (E2) and leptin were elevated, and follicular stimulating hormone (FSH) and luteinizing hormone (LH) levels were reduced significantly in ASR. Significantly negative correlations between NPY and ER or GnRH, and between leptin and FSH or LH were observed. A positive correlation existed between serum leptin and body weight. These metabolic-endocrine changes in ASR were normalized after feeding the herbal tea. Both obesity and hypogonadotropin were expressed in ASR. The abnormal ovarian hormone milieu (elevated E2 levels) may have enhanced NPY expression and resulted in less GnRH and gonadotropin secretion. The herbal tea reduced body weight and induced ovulation in ASR.
一种特殊的凉茶已被用于治疗克罗米芬抗性无排卵疾病和肥胖,特别是对多囊卵巢综合征(PCOS)伴高胰岛素血症的病例有效。研究了凉茶对雄激素绝育大鼠(ASR)肥胖和无排卵的影响。9日龄Sprague-Dawley雌性大鼠皮下注射1.25 mg丙酸睾酮,建立ASR模型。大鼠在112日龄左右被处死。ASR表现为PCO、无排卵、高食物摄入、体重升高和肥胖。免疫细胞化学表明雌激素受体(ER)主要分布在视前区(POA)含神经肽Y (NPY)神经元的细胞质中,在弓状核(ARC)合成神经肽Y的神经元的细胞核和纤维中也发现了雌激素受体(ER)的共表达。与正常对照组相比,ASR大鼠NPY表达升高,下丘脑弧中隆起(ME) ER数量减少,ME促性腺激素释放激素(GnRH)水平降低,血清雌激素(E2)和瘦素(leptin)升高,卵泡刺激素(FSH)和黄体生成素(LH)水平显著降低。NPY与ER或GnRH、瘦素与FSH或LH呈显著负相关。血清瘦素与体重呈正相关。饲喂凉茶后,ASR的代谢-内分泌变化趋于正常化。ASR中肥胖和促性腺激素均有表达。卵巢异常激素环境(E2水平升高)可能导致NPY表达增强,GnRH和促性腺激素分泌减少。凉茶可减轻ASR患者体重,促进排卵。
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引用次数: 23
Conditional knockout of mouse insulin-like growth factor-1 gene using the Cre/loxP system. 使用Cre/loxP系统条件敲除小鼠胰岛素样生长因子-1基因。
Jun-li Liu, S. Yakar, Derek Leroith
Insulin-like growth factor-1 (IGF-1) is an essential growth factor for normal intrauterine development and postnatal growth. Mice with a complete deficiency of IGF-1 (IGF-1-null mice), created by homologous recombination, were found to exhibit postnatal lethality, growth retardation, infertility, and profound defects in the development of major organ systems. Furthermore, IGF-1-null mice were resistant to growth hormone (GH) treatment in peri-pubertal somatic growth. Using the Cre/loxP-induced conditional knockout system, we generated a mouse that lacks IGF-1 specifically in the liver, the primary site of IGF-1 production. Interestingly, although circulating and serum levels of IGF-1 were decreased by approximately 75% in these mice, they exhibited no defect in growth or development. When administered exogenously, GH stimulated IGF-1 production in several extra-hepatic tissues as well as body growth. The "Somatomedin hypothesis" originally proposed that circulating IGF-1 acting in various tissues mediate the effects of GH. These striking in vivo results, obtained using homologous recombination technology, call for a major modification of the Somatomedin hypothesis. These gene targeting studies confirm that IGF-1 is essential for GH-stimulated postnatal body growth. However, liver-derived (endocrine) IGF-1 is not essential for normal postnatal growth, though it does exert a negative feedback on GH secretion. Instead, local production of IGF-1, acting in a paracrine/autocrine fashion, appears to mediate GH-induced somatic growth. This review will discuss the effects of tissue-specific IGF-1 gene deficiency created by the Cre/loxP system versus the conventional IGF-1 knockout.
胰岛素样生长因子-1 (Insulin-like growth factor-1, IGF-1)是正常宫内发育和产后生长的重要生长因子。通过同源重组产生的完全缺乏IGF-1的小鼠(IGF-1缺失小鼠)表现出出生后死亡、生长迟缓、不育和主要器官系统发育的严重缺陷。此外,igf -1缺失小鼠在青春期前期体细胞生长过程中对生长激素(GH)产生抗性。使用Cre/ loxp诱导的条件敲除系统,我们产生了在肝脏特异性缺乏IGF-1的小鼠,肝脏是IGF-1产生的主要部位。有趣的是,尽管这些小鼠的循环和血清IGF-1水平下降了大约75%,但它们的生长或发育没有出现缺陷。当外源性给药时,生长激素刺激了几种肝外组织中IGF-1的产生以及身体生长。“生长激素假说”最初提出,循环IGF-1在各种组织中作用介导生长激素的作用。使用同源重组技术获得的这些惊人的体内结果要求对生长抑素假说进行重大修改。这些基因靶向研究证实,IGF-1对gh刺激的出生后身体生长至关重要。然而,肝源性(内分泌)IGF-1对正常的出生后生长并不是必需的,尽管它确实对生长激素的分泌有负反馈作用。相反,IGF-1的局部产生,以旁分泌/自分泌方式起作用,似乎介导gh诱导的体细胞生长。这篇综述将讨论由Cre/loxP系统产生的组织特异性IGF-1基因缺陷与常规IGF-1敲除的影响。
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引用次数: 79
Mechanisms of action of conjugated linoleic acid: evidence and speculation. 共轭亚油酸的作用机制:证据和推测。
M. Pariza, Yeonhwa Park, M. Cook
Conjugated linoleic acid (CLA) has been shown to inhibit carcinogenesis and atherosclerosis, enhance immunologic function while protecting against the catabolic effects of immune stimulation, affect body composition change (reducing body fat gain while enhancing lean body mass gain), and stimulate the growth of young rats. We discuss possible biochemical mechanisms that underlie these physiological effects. We emphasize the importance of considering the effects, both individually and combined, of the two CLA isomers (cis-9, trans-11 CLA and trans-10, cis-12 CLA) that have been shown to exhibit biological activity and which appear to exert their effects via different biochemical mechanisms.
共轭亚油酸(CLA)已被证明可以抑制癌变和动脉粥样硬化,增强免疫功能同时保护免疫刺激的分解代谢作用,影响体成分变化(减少体脂增加同时增加瘦体重增加),并刺激幼龄大鼠的生长。我们讨论了这些生理效应背后可能的生化机制。我们强调考虑两种CLA异构体(顺式-9,反式-11 CLA和反式-10,顺式-12 CLA)单独和联合作用的重要性,这两种异构体已显示出生物活性,并似乎通过不同的生化机制发挥其作用。
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引用次数: 223
Anti-inflammatory effects of ergotamine in steers. 麦角胺对牛的抗炎作用。
N. Filipov, F. N. Thompson, J. A. Stuedemann, T. Elsasser, S. Kahl, L. Stanker, C. Young, D. Dawe, C. K. Smith
The objective of this experiment was to investigate whether the ergot alkaloid, ergotamine (ET), an alkaloid used to model fescue toxicosis in cattle, modifies the response of cattle to endotoxin (LPS) challenge. Steers (n = 16) were divided into the following treatment groups: control (C), ergotamine (ET), endotoxin (LPS), and ET + LPS. ET and ET + LPS groups received a single bolus intravenous injection of ET (40 microg. kg. body wt(-1)), whereas C and LPS steers received a single bolus injection of sterile vehicle. Thirty minutes after ET/vehicle administration, a single bolus intravenous injection of LPS (0.2 microg. kg. body wt(-1)) was given. Blood was collected at various time points for 48 hr post. Endotoxin increased rectal temperature (RT) and the circulating levels of tumor necrosis factor-alpha (TNF-alpha), cortisol, haptoglobin (Hp), thromboxane B(2) (TXB(2)). The circulating Hp, TNF-alpha, and TXB(2) increases were blunted by pretreatment with ET compared with ET + LPS. Ergotamine by itself increased circulating cortisol and RT, whereas it decreased serum prolactin (PRL). Therefore, whereas administration of LPS at 0.2 microg/kg to steers resulted in an expected response, the combination of ET + LPS attenuated major effects of LPS alone. Thus, acute administration of ET appeared to be anti-inflammatory as it decreased the inflammatory response to LPS, an effect likely driven at least in part by the ET-caused cortisol increase.
本试验旨在研究麦角生物碱麦角胺(ET)是否会改变牛对内毒素(LPS)的反应。麦角生物碱是一种用于模拟牛羊茅中毒的生物碱。16只实验组分为对照组(C)、麦角胺组(ET)、内毒素组(LPS)和内毒素组(ET + LPS)。ET组和ET + LPS组给予单次静脉注射ET (40 μ g)。公斤。体wt(-1)),而C组和LPS组接受单次注射无菌载体。在给药30分钟后,单次静脉注射LPS(0.2微克)。公斤。给出体wt(-1)。在48小时后的不同时间点采集血液。内毒素升高直肠温度(RT)和循环中肿瘤坏死因子- α (tnf - α)、皮质醇、触珠蛋白(Hp)、血栓素B(TXB)的水平。与ET + LPS相比,经ET预处理后,循环Hp、tnf - α和TXB(2)的增加被减弱。麦角胺本身增加循环皮质醇和RT,而降低血清催乳素(PRL)。因此,虽然以0.2微克/千克的剂量给牛LPS会产生预期的反应,但ET + LPS的组合会减弱单独使用LPS的主要影响。因此,急性给药ET似乎具有抗炎作用,因为它降低了对LPS的炎症反应,这种效果可能至少部分是由ET引起的皮质醇增加引起的。
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引用次数: 9
Detection of antigen-specific human serum proteins related to the T-cell receptor in infectious disease and in an immune response to milk proteins or chemicals. 在传染病和对牛奶蛋白或化学物质的免疫反应中与t细胞受体相关的抗原特异性人血清蛋白的检测。
C. Little, G. Georgiou, G. Fey, B. Ravindran, J. Levine, H. Ogedegbe, H. Yamase, R. Cone
A monoclonal IgG2 antibody, MG3C9-1 A12, was prepared by immunization of mice with human serum Cohn Fraction III proteins enriched for TCR Ca+ proteins. MG3C9-1 A12 bound to Mr 28,000, antigen-specific TCR Ca+, beta-, and TCR Ca+, beta+ serum proteins associated with TGF-beta1, 2. The IgG2 monoclonal antibody also bound to T-lymphocyte proteins but did not bind to B lymphocyte proteins, human albumin, IgM, IgG, IgA, or TGF-beta1, 2, 3 immunogenic peptides. Monoclonal MG3C9-1 A12 detected TCR-related proteins specific for filarial extract, milk proteins, or benzoic acid in the sera of individuals with chronic or asymptomatic filariasis, milk intolerance, or sensitivity to toluene, respectively. TCR-related serum proteins were also detected intracellularly in mononuclear cells in frozen sections of ileum from a patient with milk intolerance and reactive mesenteric lymph nodes from a patient with a gastric ulcer. The results suggest that antigen-specific TCR-related serum proteins may be elevated during an immune response to oral, environmental, or infectious stimuli.
用富含TCR Ca+蛋白的人血清Cohn Fraction III蛋白免疫小鼠制备IgG2单克隆抗体MG3C9-1 A12。mg3c9 - 1a12结合Mr 28000,抗原特异性TCR Ca+, β -和TCR Ca+, β +血清蛋白与tgf - β a1, 2。IgG2单克隆抗体也与t淋巴细胞蛋白结合,但不与B淋巴细胞蛋白、人白蛋白、IgM、IgG、IgA或tgf - β 1,2,3免疫原性肽结合。单克隆MG3C9-1 A12分别检测慢性或无症状丝虫病、牛奶不耐受或甲苯敏感患者血清中丝虫病提取物、牛奶蛋白或苯甲酸特异性tcr相关蛋白。在一名牛奶不耐受患者的回肠冷冻切片和一名胃溃疡患者的反应性肠系膜淋巴结中,也检测到细胞内单个核细胞中的tcr相关血清蛋白。结果表明抗原特异性tcr相关血清蛋白可能在口腔、环境或感染刺激的免疫反应中升高。
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引用次数: 1
Molecular genetics of the hair follicle: the state of the art. 毛囊的分子遗传学:最先进的技术。
M. V. van Steensel, R. Happle, P. Steijlen
For those who are interested in the biology of skin and its derivatives, these are interesting times indeed. In a mere 5 years, the field has been revolutionized by the application of molecular genetics to human congenital skin disorders. Where dermatology first was limited to observation and empirics, there are now DNA-diagnostics, rational drug design, and perhaps even gene therapy available soon. In particular, the study of rare human syndromes involving abnormalities of hair growth and structure has yielded new insights into the regulation of cell growth and differentiation in the hair follicle. As this structure shows a cyclic pattern of differentiation, it may give new information concerning the regulation of cell differentiation in general. This review covers the recent developments in this fast-moving field. First, we will give a short introduction to (structural) hair biology. Next, we will try to fit these data into the framework of what is already known and attempt to present a unified model for hair follicle growth and differentiation.
对于那些对皮肤及其衍生物的生物学感兴趣的人来说,这确实是一个有趣的时代。在短短5年的时间里,分子遗传学在人类先天性皮肤病上的应用已经彻底改变了这一领域。在皮肤病学最初仅限于观察和经验的地方,现在有了dna诊断,合理的药物设计,甚至可能很快就会有基因治疗。特别是,对涉及头发生长和结构异常的罕见人类综合征的研究,为毛囊细胞生长和分化的调节提供了新的见解。由于这种结构表现出一种循环的分化模式,它可能为一般的细胞分化调控提供新的信息。本文综述了这一快速发展领域的最新发展。首先,我们将简要介绍(结构)头发生物学。接下来,我们将尝试将这些数据整合到已知的框架中,并尝试为毛囊生长和分化提供一个统一的模型。
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引用次数: 18
Feeding DHEA to C57/B167 mice: the authors respond 给C57/B167小鼠喂食脱氢表雄酮:作者的反应
Bennett, Cătălina, Kumar, Milewich
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引用次数: 0
Prevention of N-methylnitrosourea-induced colon carcinogenesis in rats by oxygenated carotenoid capsanthin and capsanthin-rich paprika juice. 含氧类胡萝卜素辣椒素和富含辣椒素的辣椒汁预防n-甲基亚硝基源诱导的大鼠结肠癌。
T. Narisawa, Y. Fukaura, M. Hasebe, S. Nomura, S. Oshima, T. Inakuma
Epidemiological and animal studies have provided evidence that dietary carotenoids may reduce the risk of certain types of cancer. An inhibitory activity of oxygenated carotenoid capsanthin, a potent antioxidant, and paprika juice rich in capsanthin (3.54 mg/100 ml) against colon carcinogenesis was investigated in F344 rats. In Experiment I (short-term assay), six rats each were given a gavage of 5 mg, 0.2 mg, or 0.008 mg capsanthin six times a week for Weeks 2-6 after receiving three intrarectal doses of 4 mg N-methylnitrosourea in Week 1. The number of colonic aberrant crypt foci, preneoplastic lesions, at Week 6 was significantly fewer (by 42%) in the 0.2 mg capsanthin group, but not in other groups, than the control group. In Experiment II (long-term assay), five groups of 30 or 25 rats each received an intrarectal dose of 2 mg N-methylnitrosourea three times a week for Weeks 1-3, and had either of 10 p.p.m. or 2 p.p.m. capsanthin solutions, 1:2.5 and 1:16.7 diluted solution of paprika juice (containing 10 p.p.m. or 2 p.p.m. capsanthin), and tap water (control fluid) as drinking fluid throughout the experiment. The experimental groups were fed 0.2 mg or 0.04 mg capsanthin/day/rat. The colon cancer incidence at Week 30 was significantly lower in the highly diluted paprika juice group (40%), but not in the moderately diluted paprika juice group (60%) and the capsanthin solution groups (68% and 68%) than the control group (83%). The results suggested that paprika juice may affect colon carcinogenesis. However, capsanthin alone failed to inhibit colon tumorigenesis, in spite of suppression of aberrant crypt foci formation in the short-term assay. Further studies are needed to explain this discrepancy.
流行病学和动物研究提供的证据表明,膳食类胡萝卜素可以降低患某些类型癌症的风险。研究了含氧类胡萝卜素辣椒素(一种有效的抗氧化剂)和富含辣椒素(3.54 mg/100 ml)的辣椒汁对F344大鼠结肠癌的抑制作用。实验一(短期试验),6只大鼠在第1周接受3次n -甲基亚硝基脲4 mg直肠内灌胃后,每周灌胃6次辣椒素5 mg、0.2 mg或0.008 mg,连续第2-6周。在第6周,0.2 mg辣椒素组结肠异常隐窝灶(肿瘤前病变)的数量明显少于对照组(减少42%),但其他组没有。在实验二(长期试验)中,5组大鼠,每组30或25只,在第1-3周内,每周三次直肠内注射2mg n -甲基亚硝基脲,并在整个实验过程中分别使用下午10点或下午2点的辣椒素溶液,1:2.5和1:16.7稀释的辣椒汁溶液(含下午10点或下午2点的辣椒素)和自来水(对照液)作为饮用液体。试验组分别饲喂辣椒素0.2 mg、0.04 mg /d /只。在第30周,高度稀释的红辣椒汁组的结肠癌发病率明显低于对照组(83%)(40%),但中等稀释的红辣椒汁组(60%)和辣椒素溶液组(68%和68%)的结肠癌发病率低于对照组(83%)。结果表明,辣椒汁可能影响结肠癌的发生。然而,单独使用辣椒素不能抑制结肠肿瘤的发生,尽管在短期实验中抑制了异常隐窝灶的形成。需要进一步的研究来解释这种差异。
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引用次数: 24
The cannabinoid system and cytokine network. 大麻素系统和细胞因子网络。
T. Klein, B. Lane, C. Newton, H. Friedman
Many advances have been made in the last few years concerning our understanding of the receptors and ligands composing the cannabinoid system. Likewise, the science surrounding cytokine biology has advanced enabling us to measure these proteins more precisely as well as understand and interpret the meaning of changes in their levels. Scientists wishing to study the health consequences of smoking marijuana as well as understand the possible role of endogenous cannabimimetic ligands in immune regulation have continued to study the influence of these substances on the regulation and development of the cytokine network. Research has shown that two major cannabinoid receptor subtypes exist and that subtype 1 (CB1) is expressed primarily in the brain whereas subtype 2 (CB2) is expressed primarily in the periphery. A variety of ligands for these receptors based on the cannabinoid structure have been synthesized and studied as well as low affinity compounds, noncannabinoid ligands, and endogenous ligands derived from fatty acid eicosanoids. Highly selective receptor antagonists have also been introduced and studied. Synthetic, low affinity ligands such as (+)-HU-211 and DMH-11C have been shown to cause anti-inflammatory effects possibly through inhibiting the production and action of TNF-alpha and other acute phase cytokines. In addition, suppression of TNF and other cytokines such as GM-CSF, IL-6, IFNgamma, and IL-12 has also been seen following exposure to high affinity and psychoactive ligands such as marijuana and THC. However, some of these ligands have also been shown to increase rather than decrease interleukins such as IL-1, IL-4, IL-10, and IL-6, cytokines such as TNF-alpha, and chemokines such as IL-8, MIP-1, and RANTES. The endogenous ligand, anandamide, has been shown in culture to either suppress the proliferation response to prolactin or enhance the response to cytokines such as IL-3 and IL-6. This eicosanoid has also been shown to increase the production of interleukins and other cytokines. Cannabinoid receptors have been shown to be involved in some but not all of these effects. It is clear that psychoactive and nonpsychoactive compounds have demonstrated effects in vivo and in vitro on the production and function of a variety of cytokines. Depending upon the model system, these effects are often conflicting, and the involvement of cannabinoid receptors is unclear. However, enough evidence exists to suggest that the cannabinoid system significantly impacts the functioning of the cytokine network, and this association may provide clues to the mechanisms of certain immune diseases and form the basis for new immunotherapies.
在过去的几年里,关于我们对构成大麻素系统的受体和配体的理解取得了许多进展。同样,围绕细胞因子生物学的科学也取得了进步,使我们能够更精确地测量这些蛋白质,并理解和解释它们水平变化的意义。科学家们希望研究吸食大麻对健康的影响,并了解内源性大麻拟配体在免疫调节中的可能作用,他们继续研究这些物质对细胞因子网络的调节和发育的影响。研究表明,存在两种主要的大麻素受体亚型,其中亚型1 (CB1)主要在大脑中表达,而亚型2 (CB2)主要在外周表达。各种基于大麻素结构的受体配体以及低亲和化合物、非大麻素配体和由脂肪酸类二十烷衍生的内源性配体已经被合成和研究。高选择性受体拮抗剂也被引入和研究。人工合成的低亲和力配体如(+)-HU-211和DMH-11C已被证明可能通过抑制tnf - α和其他急性期细胞因子的产生和作用而具有抗炎作用。此外,暴露于高亲和力和精神活性配体(如大麻和四氢大麻酚)后,TNF和其他细胞因子如GM-CSF、IL-6、IFNgamma和IL-12也被发现受到抑制。然而,其中一些配体也显示出增加而不是减少白细胞介素如IL-1、IL-4、IL-10和IL-6,细胞因子如tnf - α和趋化因子如IL-8、MIP-1和RANTES。内源性配体anandamide已经在培养中被证明可以抑制催乳素的增殖反应或增强对IL-3和IL-6等细胞因子的反应。这种类二十烷也被证明可以增加白细胞介素和其他细胞因子的产生。大麻素受体已被证明参与了这些影响的一部分,但不是全部。很明显,精神活性和非精神活性化合物已经在体内和体外证明了对多种细胞因子的产生和功能的影响。根据模型系统的不同,这些影响往往是相互冲突的,大麻素受体的参与尚不清楚。然而,有足够的证据表明大麻素系统显著影响细胞因子网络的功能,这种关联可能为某些免疫疾病的机制提供线索,并形成新的免疫疗法的基础。
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引用次数: 142
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Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
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