Cyr61上调人角质形成细胞表达IL-36α的实验研究

银屑病是多种炎症因子参与的慢性炎症性皮肤疾病,其中IL-1家族分子IL-36α与银屑病发生发展密切相关。在基因敲除小鼠研究中发现,当敲除IL-36α基因后,再用咪喹莫特制备小鼠银屑病样模型时,皮损和炎症都明显减轻。我们前期研究发现促炎因子Cyr61/CCN1能通过活化角质细胞、促进趋化因子产生而加剧银屑病发生,但其是否也参与IL-36α表达与调控则未见报道。本研究采用人永生化角质形成细胞(human immortalized keratinocytes cell line,HaCaT cell)在体外研究Cyr61对IL-36α表达的调控作用。结果发现Cyr61能显著上调HaCaT细胞表达IL-36α,而且呈剂量依赖性。进一步通过siRNA干扰技术下调HaCaT细胞中Cyr61的内源性表达,发现当Cyr61表达受抑制后,IL-36α表达也被有效抑制,表明Cyr61能够介导角质细胞表达IL-36α。已有报道表明TNF-α、IL-17和IL-22能够上调角质细胞表达IL-36α,因此我们还采用TNF-α、IL-17和IL-22特异性siRNA干扰这些炎症因子的内源性表达,观察Cyr61对IL-36α的作用。结果表明这些因子被干扰后并不影响Cyr61对IL-36α表达的影响,说明Cyr61能直接促进IL-36α表达。本研究的结果提示Cyr61/CCN1还可能通过上调IL-1家族分子IL-36α而参与银屑病发生。     

CCL20/CCR6轴在银屑病发病过程中的作用

银屑病是一种以Th17淋巴细胞异常活化和浸润为主要特征的慢性炎性反应皮肤病。调节Th17迁移的趋化因子/趋化因子受体CCL20/CCR6轴在银屑病的发病机制中可能处于关键地位,因而成为新的治疗靶标。CCL20/CCR6轴异常表达,导致Th17细胞异常迁移,并激活Th17细胞与角质形成细胞间的循环刺激网络,是银屑病皮损炎症反应持续存在的重要基础。     

银屑病皮损中CXCL11/I-TAC及其受体CXCR3的表达

CXCL11/I-TAC(Interferon-inducible T Cell α-chemoattractant)是一种Ⅰ型趋化因子,可以特异性地趋化表达CXCR3的Th1细胞[1,2].有研究表明,Th1占主导的皮肤病如银屑病皮损中,CXCL11/I-TAC mRNA主要在基底层角质形成细胞中高表达;CXCR3主要表达于真皮炎症区大部分T细胞[3],提示CXCL11/I-TAC及其受体CXCR3在该类慢性炎症性皮肤病的T细胞浸润的募集和维持中起重要作用.Th1细胞因子IFN-γ和TNF-α在Th1型皮肤病皮损中也高表达[4,5].     

Th17细胞与角质形成细胞相关细胞因子在银屑病中的作用

银屑病的发病机制主要表现为以T细胞介导的以角质形成细胞（KC）为靶点的免疫应答反应。在T细胞因子作用下，KC可能会出现异常的增殖和分化，其通过表达细胞因子参与T细胞的记忆和活化。Th17细胞是一种新发现的CD4^＋T细胞亚群，因其分泌IL-17（IL-17A）而命名。IL-17促进KC产生VEGF、IL-8、GM．CSF、TNF—α、CXCL10等细胞因子可能会诱发和加重银屑病。     

丹皮酚通过STAT3通路抑制IL-17A诱导的角质形成细胞活性和细胞因子分泌

目的:观察丹皮酚对白细胞介素17A(IL-17A)诱导的人角质形成细胞活性、细胞因子分泌及相关信号转导通路的影响。方法:采用IL-17A(200μg/L)刺激体外培养的HaCaT细胞,同时加入不同浓度(200 mg/L和100 mg/L)丹皮酚共同培养24 h。采用CCK-8法测定细胞的活力;CBA法测定Th1/Th2/Th17类炎症细胞因子的变化;ELISA法测定炎症细胞因子IL-23的水平;real-time PCR法测定炎症因子IL-23、IL-6、CXCL2、CXCL8、CCL20和STAT3的mRNA表达;Western blot法测定信号转导通路中STAT3和ERK1/2的蛋白水平。结果:丹皮酚能够显著抑制IL-17A诱导的HaCaT细胞的活力(P<0.05);丹皮酚能够减少IL-6的分泌,同时,能够降低IL-23、CXCL2、CXCL8和CCL20的mRNA表达,并对细胞内STAT3的mRNA和蛋白表达有一定的抑制作用,而对ERK1/2的蛋白水平无显著影响。结论:丹皮酚能够抑制IL-17A诱导的HaCaT细胞的活性和细胞因子的分泌,其作用机制可能与STAT3通路有关...     

大疱性类天疱疮皮损中Th1/Th2趋化因子及其受体的表达

目的:研究Th1趋化因子CXCL9/MIG、CXCL10/IP-10、CXCL11/I-TAC和Th2型趋化因子CCL22/MDC及其受体CXCR3、CCR4在大疱性类天疱疮(BP)皮损中的表达。方法:应用免疫组化方法检测30例BP患者皮损及20例正常皮肤中CX-CL9、CXCL10、CXCL11、CCL22、CXCR3和CCR4的表达。结果:BP皮损中4种趋化因子及其受体的表达均高于正常皮肤。其中,Th1趋化因子CXCL9、CXCL10和CXCL11及其受体CXCR3的阳性率分别为50%(15/30)、46.7%(14/30)、46.7%(14/30)和53.3%(16/30),Th2趋化因子CCL22及其受体CCR4的阳性率分别为66.7%(20/30)、56.7%(17/30)。正常对照中CXCL9、CX-CL10、CXCL11及其受体CXCR3的阳性率分别为10.0%(2/20)、10.0%(2/20)、15.0%(3/20)和15.0%(3/20),CCL22及其受体CCR4的阳性率分别为20.0%(4/20)和25.0%(5/20)。结论:Th1趋化因子CXCL9、CXCL10、CXCL11和Th2趋化因子CCL22及其受体CXCR3和CCR4在BP皮损中表达升高,提示它们可能在BP的发病机制中起一定作用。     

免疫性血小板减少症Th1和Th2趋化因子及其受体表达的研究

目的免疫性血小板减少症(immune thrombocytopenia,ITP)是一种获得性自我免疫紊乱导致的出血性疾病,本文旨在研究ITP患者体内T-helper 1(Th1)趋化因子CCL5、CXCL11及其受体CCR5、CXCR3和Th2趋化因子CCL11及其受体CCR3的表达变化,以探讨趋化因子及其受体在ITP免疫异常中的作用。方法选择28名活动性ITP患者为研究对象,随机选取21名与ITP患者相匹配的健康人作对照组。以酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测ITP患者和对照组血浆中CCL5、CXCL11和CCL11的含量,采用实时聚合酶链式反应(real-time polymerase chain reaction,RT-PCR)检测外周血单个核细胞(PBMC)CCL5、CXCL11、CCL11、CCR5、CXCR3以及CCR3 mRNA的表达。结果 Th1相关趋化因子CCL5和Th2相关趋化因子CCL11在活动性ITP患者血浆中含量均低于正常对照组(P0.05),而Th1趋化因子CXCL11升高(P0.05);ITP患者PBMC的CXCL11 mRNA表达高于对照组,CCL11 mRNA表达低于对照组(P0.05),而CCL5 mRNA在ITP组与对照组差异无显著性(P0.05)。ITP患者血浆中Th1相关趋化因子受体CCR5和CXCR3表达量高于对照组(P0.05),Th2相关趋化因子受体CCR3降低(P0.05)。经过糖皮质激素等治疗有效的22例患者,Th1趋化因子CXCL11、趋化因子受体CCR5和CXCR3均下降(P0.05),血浆CCL5含量回升,但是仍低于对照组(P0.05);而Th2相关趋化因子CCL11及其受体CCR3均回升(P0.05)。结论 Th1/Th2相关趋化因子及其受体的异常表达可能参与了ITP的免疫紊乱,是ITP发病因素之一;阻断Th1相关趋化因子与其受体的作用途径,可望成为ITP的生物调控靶点。     

microRNA-155通过靶向抑制C/EBP-β和TAB2调控趋化因子的表达

目的明确microRNA(miR)-155对趋化因子CCL5、CXCL9、CXCL10、CCL20和CCL22表达的调控作用及其靶基因。方法培养RAW264.7细胞,向细胞内转染寡聚核苷酸(包括miR-ctrl、miR-155 mimics和miR-155 inhibitor)或靶基因保护子(包括C/EBP-β-TP~(miR-155)、TAB2-TP~(miR-155)和SOCS1-TP~(miR-155)),并用1μg/ml LPS刺激细胞活化,用RT-PCR、ELISA和Western blotting方法检测趋化因子及miR-155靶基因表达情况。结果 (1)miR-155抑制LPS活化的RAW264.7细胞分泌CXCL9、CXCL10和CCL20(P0.05),而促进上述细胞分泌CCL22(P0.05);(2)C/EBP-β和TAB2分别是miR-155调控CXCL9和CXCL10表达的靶基因。结论 miR-155可通过调控趋化因子的表达参与调控免疫炎症反应。     

CXCL10在Graves’病发病中的作用

CXC趋化因子配体-10（CXCL10）属于CXC家族的非ELR亚组趋化因子, 参与多种疾病的发生,主要介导Th1型炎症反应,趋化单核细胞和T细胞,与变态免疫发生、自身免疫性疾病等有关。CXCL10与Graves’病之间关系的研究将为深入探讨Graves’病的发病机制及诊断治疗提供新的思路。     

组蛋白去乙酰化酶1通过NF-κB调控炎症性滑膜细胞表达Cyr61

本研究探讨组蛋白去乙酰化酶(histone deacetylase enzyme,HDAC)在IL-17上调类风湿性关节炎(rheumatoid arthritis,RA)滑膜细胞Cyr61表达过程中的调控机制。通过real-time PCR分别检测了滑膜组织和细胞中的HDAC表达格局,HDAC抑制剂曲古抑菌素(trichostatin,TSA)和尼克酰胺(nicotinamide,NAM)作用于滑膜细胞及其相关信号通路变化后IL-17上调Cyr61的表达格局。结果显示:RA病人滑膜组织和细胞中高表达HDAC1,并且IL-17刺激又能促进滑膜细胞的HDAC1表达升高。TSA能上调IL-17诱导滑膜细胞Cyr61的表达,而NAM不能。加入NF-κB特异性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)能够明显的抑制TSA对Cyr61的上调作用。以上结果提示HADC1通过作用于转录因子NF-κB参与了IL-17上调滑膜细胞表达Cyr61的过程。     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Cerebellar noradrenergic systems in aging: studies in situ and in in oculo grafts

Age-related changes in noradrenergic function in the rat cerebellum were examined using electrophysiological and electrochemical techniques. Sprague-Dawley and Fischer 344 rats showed subsensitivity to norepinephrine (NE) locally applied onto cerebellar Purkinje neurons. The modulatory actions of NE on Purkinje cell-evoked activity was also examined. In young rats NE preferentially inhibits spontaneous activity more than evoked excitations when compared to control. These modulatory actions of NE are not seen in senescent Fischer 344 rats. The intrinsic vs. extrinsic influences determining the loss of efficacy to NE were examined using three groups of rats with in oculo cerebellar grafts. The first group had young grafts grown in young hosts and these grafts showed a potent response to perfused NE. The second group, old grafts in old hosts, showed a diminished responsiveness to NE with respect to the first group. The third group consisted of young grafts in old hosts. These grafts demonstrated a responsiveness to NE that was indistinguishable from those in the first group. The integrity of the presynaptic NE fibers was examined in the grafts using electrochemical techniques. No difference in the release of NE was observed in the old grafts. Taken together, these results suggest a loss of postsynaptic NE function that is intrinsically determined. The change in NE modulation could influence information processing within the aged cerebellar cortex. This deficit could underlie behavioral changes seen in senescence.