连续观察兔油酸ARDS模型稳定性及血L-1、IL-8近期变化

目的:探讨油酸(OA)构建兔急性呼吸窘迫综合征(ARDS)模型3天内的稳定性及血浆炎症因子IL-1、IL-8含量变化的意义。方法:健康新西兰大耳白兔30只随机分为5组,每组6只,实验组(n=24)耳缘静脉注射油酸(0.1mL/kg)建立ARDS模型,对照组(n=6)注射等量生理盐水。分别检测对照组6h和实验组6h、24h、48h、72h(n=6)动脉血PH值、PaO2、PaO2/FiO2、PaCO2、肺湿/干重比值(W/D),ELISA法检测血浆细胞因子IL-1、IL-8含量,HE染色观察肺组织病理学改变。结果:和对照组比较,实验组血中细胞因子IL-1在6h、24h组升高;细胞因子IL-8在6h组、24h组、48h组升高。6h组、24h组、48h组氧合指数<200mmHg。结论:兔油酸ARDS模型48h内稳定,炎性细胞和IL-1、IL-8可能是导致ARDS的发生和发展主要原因之一。     

油酸致兔ARDS模型长期效果的多因素析评

目的:研究油酸致ARDS模型对疾病的长期模拟效果,并探讨内在机制。方法:选择健康新西兰大白兔30只,经左侧耳缘静脉按油酸0.1 ml/kg的剂量缓慢注入,观察动物呼吸、心率变化,测定氧合指数(PaO2/FiO2)、动脉氧分压、二氧化碳分压。分别于注射油酸后6小时、24小时、48小时以及72小时处死动物,收集静脉血及肺泡灌洗液(BALF),ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)变化。H-E染色镜下观察肺部病理改变,计算肺组织含水量以判断肺损伤程度。结果:①所有模型动物在6小时内均出现ARDS表现。②6h组、24h组以及48h组氧合指数(PaO2/FiO2)与正常对照组相比均明显降低(P<0.05),且符合ARDS诊断标准。72h组氧合指数(PaO2/FiO2)虽然也明显降低,但未达到ARDS的诊断标准。③血浆中TNF-α与IL-6明显升高(P<0.05),于致伤后72小时后有所恢复,但仍高于正常。BALF中TNF-α也出现相同变化趋势,而IL-6则在试验期间持续高表达。④镜下可见两肺充血、出血,肺泡及肺间质水肿,透明膜形成,大量中性粒细胞浸润,终末支气管上皮细胞变性坏死,双肺含水...     

TNF-α、IL-6、IL-8和sICAM-1与嗜肺军团菌感染关系的研究

目的探讨细胞因子IL-6、IL-8、TNF-α和黏附分子sICAM-1在嗜肺军团菌（Lp）感染者血清中的表达情况及其临床意义。方法用ELISA法检测30例Lp感染者和40例健康体检者血清中IL-6、IL-8、TNF-α、sICAM-1的含量并进行对比。结果Lp感染者血清中TNF-α、IL-6、IL-8、sICAM-1均表现出急性期〉恢复期,且急性期TNF-α、IL-8、sICAM-1浓度均较正常对照组明显增高,P〈0．05,IL-6与IL-8、TNF-α、sICAM-1及TNF-α与sICAM-1的改变存在明显的正相关。结论Lp感染者血清中IL-6、IL-8、TNF-α、sICAM-1含量出现表达异常,并随着病情程度的不同改变不同,对临床病情的监测、治疗、疗效判断、预后估计有重要的临床意义。     

慢性阻塞性肺病患者急性加重期外周血IL-8、TNF-alpha及IGF-I表达变化 的意义

目的：研究慢性阻塞性肺病（COPD）患者急性加重期外周血白细胞介素-8（IL-8）、肿瘤坏死因子-a（TNF-a）及胰岛素样生长 因子-I（IGF-I）表达变化的临床意义。方法：选取2013 年12 月-2014 年12月我院收治的COPD 急性加重患者100 例为观察组, 选取同期健康体检者100 例为对照组,检测观察组患者治疗前、治疗稳定后及对照组外周血IL-8、TNF-alpha及IGF-I水平。结果：观 察组患者治疗前外周血IL-8、TNF-alpha及IGF-I水平显著高于治疗稳定后,差异有统计学意义（P＜ 0.05）;观察组患者治疗稳定后外 周血IL-8、TNF-alpha及IGF-I水平显著高于对照组,差异有统计学意义（P＜0.05）。结论：COPD 急性加重期外周血IL-8、TNF-琢及 IGF-I水平显著增高,治疗稳定后其水平显著降低,IL-8、TNF-alpha及IGF-I水平对COPD 的诊断和治疗具有重要意义。     

姜黄素干预油酸诱导的ALI/ARDS大鼠模型对NF-κB、TNF-α和IL-6的影响

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)发病机制的大量研究表明核因子κB(nuclear factor kappa B,NF-κB)激活是其发生、发展的中心环节.姜黄素作为治疗ALI/ARDS的可能潜在性药物的作用和机制尚不明晰.该研究将大鼠随机分为正常组(C组)、模型组(M组)、二甲基亚砜(D组)和姜黄素治疗组(T组),通过大鼠ALI/ARDS模型,利用光镜H.E.染色观察肺部组织形态学变化,比较肺湿/干重(W/D),酶联免疫吸附法(ELISA)测定支气管肺泡灌洗液(bronchoalveolarlavage fluid,BALF)中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)含量动态变化,以及间接免疫荧光染色和免疫印记(Western blot)检测肺组织NF-κB蛋白水平变化,分析姜黄素对ALI的保护作用以及NF-κB、TNF-α和IL-6水平的影响.研究发现造模后4 h,M组BALF中TNF-α、IL-6升高并达高峰(P<0.05);姜黄素干预后,T组肺组织病理学改变减轻,BALF中蛋白渗出、TNF-α和IL-6明显减少(P<0.05).间接免疫荧光检测和Western blot结果显示C组大鼠肺组织蛋白抽提物中存在少量NF-κB蛋白,而M组明显升高,在4 h时达高峰,这一峰值出现时间与造模后肺内炎性损伤因子TNF-α、IL-6释放的高峰时间相吻合.姜黄素治疗后T组肺组织提取物NF-κB水平显著低于M组,且在12 h达高峰(P<0.05).D组与M组各检测指标未见差异(P>0.05).结果表明姜黄素能明显抑制ALI/ARDS后的NF-κB的表达,抑制炎性反应,对ARDS可能具有潜在治疗价值.     

中药灌肠对宫颈癌急性放射性直肠炎患者临床疗效及血清IL-1β、IL-8、TNF-α水平的影响

摘要 目的：探讨中药灌肠对宫颈癌急性放射性直肠炎（ARP）患者临床疗效及血清白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白介素-8（IL-8）水平的影响。方法：选取2021年3月-2023年3月期间在邵阳市中心医院收治行放疗的宫颈癌ARP患者180例,采用随机数字表法将患者分为A组（常规治疗,n=90）和B组（A组的基础上接受中药灌肠,n=90）。观察两组临床疗效、放射损伤疗效、中医证候积分和IL-1β、IL-8、TNF-α水平变化情况,并对比不同放射性直肠炎分级患者的血清IL-1β、IL-8、TNF-α水平。结果：B组的临床总有效率高于A组（P<0.05）。两组治疗后黏液血便、腹痛、里急后重、稀便或便秘、肛门灼痛坠痛、口干口苦、尿赤等证候积分下降,且B组低于A组（P<0.05）。B组的放射损伤总有效率高于A组（P<0.05）。放射性直肠炎分级III级、Ⅱ级血清IL-1β、IL-8、TNF-α水平高于I级,且III级高于Ⅱ级（P<0.05）。两组治疗后血清IL-1β、IL-8、TNF-α水平下降,且B组低于A组（P<0.05）。结论：中药灌肠治疗宫颈癌ARP患者,可提高临床疗效,改善临床症状,可能与改善血清IL-1β、IL-8、TNF-α水平有关。     

结直肠癌患者手术前后血清TNF-α, NO, IL-1β、IL-6水平变化及临床意义

目的:探索结直肠癌患者术前术后肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、一氧化氮(nitric oxide,NO)、白细胞介素-1β(Interleukin-1Beta,IL-1β)、白细胞介素-6(interleukin-6,IL-6)表达水平的变化及其临床意义。方法:对本院75例结直肠癌患者分别采用硝酸还原法及双抗夹心ELISA法检测手术前后NO及TNF-α、IL-1β、IL-6表达水平的变化,同时将其与43例健康体检者相比较。结果:结直肠癌患者手术前血清中TNF-α、IL-1β、IL-6浓度(19.45±4.09,3.91±0.25,15.93±1.00)明显高于正常对照组(P0.05),而NO浓度(27.5±5.5)明显低于正常对照组(P0.05),手术治疗后7天,TNF-α、IL-1β、IL-6血清含量(12.31±3.89,1.41±0.33,9.30±2.11)明显降低(P0.05),而NO含量恢复正常水平。结论:血清中TNF-α、NO、IL-1β、IL-6浓度与结直肠癌密切相关,对TNF-α、NO、IL-1β、IL-6浓度进行联合诊断可作为结直肠癌早期诊断的参考指标。     

脾虚大鼠脑内IL-1β、IL-2 表达的变化及益气扶正中药的干预研究*

目的:研究脾虚模型大鼠脑内白细胞介素1 β(IL-1β)、白细胞介素2(IL-2)的活性表达,以及扶正益气中药的干预作用.方法:40只大鼠随机分成4组,正常组、模型组、治疗1组(四君子汤组)、治疗2组(玉屏风散组),每组各10只.采用苦降泻下、饮食失节加劳倦过度法建立大鼠脾虚模型,采用免疫组化法检测下丘脑腹侧核、海马CA1区的IL-1β和IL-2表达变化与四君子汤玉屏风散的治疗作用.结果:IL-1β在海马CA1区和下丘脑腹侧核表达明显降低,IL-2在海马CA1区和下丘脑腹侧核表达明显降低;四君子汤治疗组IL-1β和IL-2在上述脑区表达明显上升;玉屏风散治疗组IL-1β和IL-2在上述脑区表达呈紊乱变化现象.结论:益气扶正中药四君子汤、玉屏风散可能通过影响免疫器官、调控细胞因子IL-1β和IL-2活性表达而调节机体免疫功能.     

弥漫性轴索损伤患者血清MBP、IL-1β、IL-8及TNF-α水平的表达及临床意义

目的:探讨弥漫性轴索损伤(DAI)患者血清髓鞘碱性蛋白(MBP)、白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)水平的表达及临床意义。方法:选取2015年12月-2018年1月我院神经外科收治的DAI患者90例作为观察组,另选取在我院体检的健康志愿者30例作为对照组,并根据格拉斯哥昏迷评分(GCS)将观察组患者分为重度组(42例)、中度组(30例)、轻度组(18例)。对比观察组和对照组血清MBP、IL-1β、IL-8及TNF-α水平,比较观察组患者不同严重程度、伤后不同时间血清MBP、IL-1β、IL-8及TNF-α水平。结果:观察组患者血清中的MBP、IL-1β、IL-8及TNF-α水平显著高于对照组(P0.05)。重度组患者血清MBP、IL-1β、IL-8及TNF-α水平显著高于中度组和轻度组,且中度组显著高于轻度组(P0.05)。伤后不同时间观察组患者血清MBP、IL-1β、IL-8及TNF-α水平整体比较差异均有统计学意义(P0.05);其中MBP水平在伤后前期到伤后3d持续升高(P0.05);IL-1β、IL-8、TNF-α水平在伤后前期到伤后2d持续升高,在伤后3d呈下降趋势(P0.05)。结论:DAI患者血清MBP、IL-1β、IL-8及TNF-α水平偏高,临床通过检测这四种血清指标水平,有助于评估患者的病情。     

血清TGF-β1、BMP-7、IL-6及TNF-α与新生儿呼吸窘迫综合征的关系研究

目的:探讨新生儿呼吸窘迫综合征(NRDS)患儿血清中转化生长因子β1(TGF-β1)、骨形态发生蛋白-7(BMP-7)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化及与病情严重程度的相关性。方法:选取2017年2月至2019年2月在本院出生的75名NRDS早产儿,根据出生后12 h内是否接受肺表面活性物质(PS)治疗分为PS组(n=37)和非PS组(n=38),同期选择36例非NRDS早产儿作为对照组。比较出生后不同时间点各组早产儿血清四种细胞因子水平,Spearman相关性分析四种细胞因子与病情严重程度的相关性。结果:PS组患儿出生后0、1、3 d血清四种细胞因子均呈先升高后降低趋势(P0.05),血清TGF-β1、BMP-7水平在出生后1d和3d高于对照组(P0.05),血清IL-6、TNF-α始终高于对照组(P0.05);非PS组患儿出生后0、1、3、7 d血清TGF-β1、BMP-7、IL-6、TNF-α均持续升高(P0.05),且始终高于对照组(P0.05),血清TGF-β1、BMP-7水平在出生后3 d和7 d高于PS组,血清IL-6、TNF-α在出生后7 d高于PS组(P0.05)。IL-6、TNF-α水平随NRDS早产儿病情分级的提高而升高(P0.05),Spearman相关性分析结果显示,血清TNF-α、IL-6水平与病情严重程度呈正相关(均P0.05)。结论:NRDS早产儿血清TGF-β1、BMP-7、IL-6、TNF-α水平明显升高,经PS治疗后,NRDS早产儿炎性因子水平明显降低,检测IL-6、TNF-α水平有助于评估NRDS早产儿的病情。     

Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma

INTRODUCTION: Interleukin-8 (IL-8) is regarded as one of the most important mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS). However, knowledge regarding the influence of genetic variations within the IL-8 gene either on the development of ARDS or on IL-8 production in the traumatic setting is sparse. PATIENTS AND METHODS: In this prospective cohort study, patients were included if the following criteria were fulfilled: Injury Severity Score (ISS) >16, age 18-60 years and a survival >48 h after injury. Systemic IL-8 concentrations and the polymorphisms (IL-8-251A/T) were determined. Patients were separated according to the development of ARDS (group +ARDS vs. group -ARDS) and the genotypes of the IL-8-251A/T polymorphism (genotypes A/A, A/T and T/T). RESULTS: Group +ARDS demonstrated significantly higher IL-8 plasma concentrations from day 3 until the end of the observation period compared to group -ARDS. In addition, duration of mechanical ventilation and length of stay in the ICU were significantly longer in this group. Furthermore, a significant association between the IL-8-251A allele and IL-8 production (day 4-8) was observed. Genotype A/A showed a significantly longer duration of mechanical ventilation compared to genotype T/T. A trend towards an association between the IL-8-251A allele and an increased incidence of posttraumatic ARDS was observed (p=0.08). CONCLUSION: This data reaffirms a central role of IL-8 in the pathogenesis of ARDS. Furthermore, it points towards a genetic predisposition for posttraumatic IL-8 synthesis which might also be associated with the development of posttraumatic ARDS.     

急性呼吸窘迫综合征临床治疗观察及预后影响因素分析

目的:观察急性呼吸窘迫综合征临床治疗效果,并对预后影响因素进行分析。方法:回顾性分析2006年3月~2011年10月在我院接受治疗的56例急性呼吸窘迫综合征患者的临床资料,使用SPSS12.0进行统计分析,并进行多因素Logistic回归分析。结果:采用以PEEP为主的综合治疗,并联合使用血必净注射液和乌司他丁,治疗ARDS病死率为26.8%;预后影响因素中ARDS并发MODS、APACHEⅡ评分和发病至接受治疗时间具有显著意义。结论:该治疗方法病死率较低,效果良好;ARDS并发并发MODS、APACHEⅡ评分和发病至接受治疗时间是影响ARDS患者的病死预后主要因素。     

细胞因子在ARDS发病机制中的作用

细胞因子是由多种细胞产生的多肽或低分子糖蛋白,在人体内含量极微,在pg水平就发挥作用。作为特异性免疫反应和非特异性免疫反应的蛋白质,细胞因子以自分泌、旁分泌、或内分泌方式产生,与相应的细胞表面受体结合,在局部或全身发挥复杂的生物学效应,它们的代谢异常和疾病的发生、发展有着密切的关系。有些细胞因子已应用于临床的生物学治疗,具有深远的临床应用价值,故对细胞因子的研究将是一个越来越重要的课题。急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)发病机制错综复杂,大量临床和实验室研究证明多种效应细胞释放的炎症介质是造成ARDS的"中心环节",其中TNF-α、IL-1、IL-8、IL-10、CXC趋化因子等细胞因子在ARDS发病中的作用尤为重要。本文就细胞因子在ARDS发病机制中的作用做一综述。     

LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium.

We have previously reported the TLR4 expression in human intestinal lymphatic vessels. In the study here, microarray analysis showed the expression of the TLR4, MD-2, CD14, MyD88, TIRAP, TRAM, IRAK1, and TRAF6 genes in cultured human neonatal dermal lymphatic microvascular endothelial cells (LEC). The microarray analysis also showed that LEC expressed genes of IL-6, IL-8, VCAM-1, and ICAM-1, and the real-time quantitative PCR analysis showed that mRNA production was increased by lipopolysaccharide (LPS). The LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 production in LEC was suppressed by the introduction of TLR4-specific small interfering RNA, and also by anti-TLR4, nobiletin, and CAPE pretreatment. These findings suggest that LEC has TLR4-mediated LPS recognition mechanisms that involve at least activation of NF-kappaB, resulting in increased expression of IL-6, IL-8, VCAM-1, and ICAM-1. Both the LPS effect on the gene expression and also the suppression by nobiletin and CAPE pretreatment on the protein production were larger in IL-6 and in VCAM-1 than in IL-8 and in ICAM-1 in LEC. The signal transduction of NF-kappaB and AP-1-dependent pathway may be more critical for the expression of IL-6 and VCAM-1 than that of IL-8 and ICAM-1 in LEC.     

丙戊酸钠对LPS诱导的急性呼吸窘迫综合征小鼠的治疗作用

为了探讨丙戊酸钠(valproic acid,VPA)对急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)小鼠治疗作用及分子机制,本研究将30只雌性C57BL/6小鼠分为空白组、LPS组、LPS+VPA组,LPS+VPA组小鼠造模前腹腔预注射VPA,以LPS气管内注射诱导ARDS小鼠模型,6 h后检测各组小鼠肺水肿(湿重/干重),检测各组小鼠血液SOD和MDA水平;通过ELISA检测各组小鼠肺泡灌洗液中TNFα和IL-1β水平,Western blotting检测各组小鼠NF-κB p65和p-H2A.X蛋白表达水平。研究结果表明:与空白组相比,LPS组小鼠肺水肿显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠肺水肿显著降低,差异具有统计学意义(p<0.01)。ELISA结果显示,与空白组比较,LPS组小鼠肺组织TNFα和IL-1β含量显著升高,与LPS组比较,LPS+VPA组小鼠肺组织TNFα和IL-1β含量显著降低,差异具有统计学意义(p<0.01)。与空白组比较,LPS组小鼠血液SOD活性显著降低,MDA含量显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠血液SOD活性显著升高,MDA含量显著降低。Western blotting结果显示,与空白组比较,LPS组小鼠肺NF-κB p65和p-H2A.X蛋白表达显著升高,与LPS组比较,LPS+VPA组和阳性组小鼠肺NF-κB p65和p-H2A.X蛋白表达显著降低,差异具有统计学意义(p<0.01)。本研究初步表明:VPA能够抑制NF-κB通路,抑制小鼠氧化应激和炎症反应,保护ARDS小鼠肺组织。     

低容量负荷对创伤后ARDS肺功能的保护作用研究

目的：观察低容量负荷对创伤后急性呼吸窘迫综合征(ARDS)肺功能的保护作用。方法：165 例创伤后ARDS患者随机分为 液体控制组和对照组,用脉搏指示连续心输出量监测(PiCCO)指导液体控制,观察中心静脉压(CVP)、肺动脉楔压(PAWP)、氧合指 数(PaO2/FiO2)、肺泡- 肺动脉氧分压差,测定肺泡灌洗液中白细胞介素6(IL-6)水平、血清的肺泡表面活性蛋白D(SP-D)水平的变 化,检测呼吸机脱机时间,评估两组患者肺功能的恢复情况。结果：液体控制组血管外肺水肿指数(EVLWI)、CVP、PWAP、IL-6、 SP-D 以及肺泡-动脉氧分压差均较对照组明显下降(P<0.05),动脉血气氧分压、氧合指数较均对照组明显升高(P<0.05),机械通气 支持时间较对照组明显缩短(P<0.05)。结论：严格的液体控制可有效降低人体的容量负荷,有效促进创伤后ARDS 肺损伤和肺功 能的恢复,这可能与低容量负荷能够降低炎症反应、促进肺泡复张和改善氧合效率有关。     

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.     

House dust mite, Dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human monocytic THP-1 cells

The house dust mite (Dermatophagoides pteronissinus) plays an important role in the pathogenesis of allergic diseases, including atopic dermatitis, and asthma. Monocyte chemotactic protein 1 (MCP-1/CCL2)/IL-6/IL-8 (CXCL8) plays a pivotal role in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The aim of this study was to investigate the effect of D. pteronissinus extract (DpE) on expression of MCP-1/IL-6/IL-8 mRNA and protein and the signal transduction in the human monocytic cell line, THP-1. The mRNA and protein expression of MCP-1/CCL2, IL-6, and IL-8 were elevated by DpE in a time and dose-dependent manner in THP-1 cells. The increased expression of MCP-1, IL-6, and IL-8 was not affected by aprotinin (serine protease inhibitor) or E64 (cysteine protease inhibitor). We found that MCP-1 and IL-6 expression due to DpE was related to Src, protein kinase C δ (PKC δ), extracellular-signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and IL-8 expression was involved in Src family tyrosine kinase, PKC δ, ERK. DpE increased the phosphorylation of ERK and p38 MAPK after 5 min and peaked at 30 min. The activation was significantly blocked by PP2, an inhibitor of Src family tyrosine kinase and rottlerin, an inhibitor of PKC δ (p < 0.01). DpE increases MCP-1, IL-6, and IL-8 expression and transduces its signal via Src family tyrosine kinase, PKC, and ERK in a protease-independent manner. This finding may contribute to the elucidation of the pathogenic mechanism triggered by DpE .