IL-23研究进展

IL 2 3是新近发现的一种促炎性细胞因子 ,隶属于IL 12分子家族。类似于IL 12 ,IL 2 3是由两种亚单位 (p4 0和p19)通过二硫键形成的异二聚体分子 ,二者的生物学功能也有很多相似之处 ,但并不完全相同 ,提示IL 2 3在维护机体内环境的稳定以及病理条件下免疫系统的激活等方面发挥着独特的生物学作用     

IL—23研究进展

IL-23是新近发现的一种促炎性细胞因子，隶属于IL-12分子家族。类似于IL-12，IL-23是由两种亚单位(p40和p19)通过二硫键形成的异二聚体分子，二者的生物学功能也有很多相似之处，但并不完全相同，提示IL-23在维护机体内环境的稳定以及病理条件下免疫系统的激活等方面发挥着独特的生物学作用。     

IL-4、IL-10和抗IL-12受体β1 mAb抑制IL-23诱导正常人记忆T细胞 IFN-γ产生

目的 探讨重组人白介素23（IL-23）是否能够诱导正常人T细胞IFN-γ的产生,作用的靶细胞亚群和调节因素。方法 正常人PBMC在抗CD3（anti-CD3）单克隆抗体或anti-CD3和抗CD28（anti-CD28）单克隆抗体刺激的条件下与IL-23进行培养,采用酶联免疫吸附试验（ELISA）检测细胞培养液中IFN-γ的水平;同时采用流式细胞仪,在单个细胞水平上分析IL-23诱导PBMC IFN-γ表达的T细胞亚群。结果 在未经任何刺激的情况下,PBMC产生很低或不产生IFN-γ。IL-23呈剂量依赖方式促进由anti-CD3活化的PBMC IFN-γ产生。细胞亚群分析的结果表明,IL-23诱导记忆CD4^＋和CD8^＋T细胞表达IFN-γ,对活化的CD4^＋T细胞作用较为明显。Th2细胞因子（IL-4、IL-10）和抗IL-12受体β1 mAb（IL-12Rβ1）抑制IL-23诱导T细胞IFN-γ产生。结论 IL-23促进活化的记忆CD4^＋和CD8^＋T细胞IFN-γ的产生。Th2细胞因子和抗IL-12Rβ1 mAb抑制由IL-23诱导IFN-γ产生,提示这些细胞因子和抗体对IL-23引起的自身免疫病具有拮抗作用。     

IL-23及其受体IL-23R研究的新进展

IL-23是一个山p19和IL-12p40组成的异源二聚体分子,为IL-12细胞因子家庭的新成员。IL-23除了与IL-12共用受体亚单位IL-12Rβ1,还有一个自身特有的受体亚单位“IL-23R”。与IL-12不同,IL-23下游主要激活的不是stal4同源二聚体。IL-23作为前炎症症因子发挥作用,主要作用于记忆性T细胞,还具有潜在的抗肿瘤作用。     

IL-23与IL-12诱导NK细胞功能的异同及机制初探

目的探讨细胞因子IL-23与IL-12对NK细胞功能的影响及可能的机制。方法密度梯度离心法分离人外周血单个核细胞(PBMCs)或磁珠纯化NK细胞,不刺激或用IL-23或IL-12刺激,用流式细胞术和ELISA法检测NK细胞产生IFN-γ的情况;以K562或Jurkat细胞作为靶细胞,用流式细胞术检测NK细胞的杀伤功能并分析NK细胞在不同的刺激条件下杀伤相关分子的表达情况及pSTAT的表达情况。结果与未刺激组相比,IL-23和IL-12均可以诱导NK细胞呈剂量和时间依赖方式产生IFN-γ;但IL-12而非IL-23可以增强NK细胞对靶细胞K562或Jurkat细胞的杀伤功能。进一步研究表明,IL-12而非IL-23可以诱导杀伤相关分子TRAIL及CD107a/b的表达。此外,IL-12诱导NK细胞表达更高水平的pSTAT4,而IL-23诱导NK细胞表达更高水平的pSTAT3。结论与IL-12相比,IL-23亦可以诱导NK细胞产生细胞因子但不能增强NK细胞的杀伤功能,IL-23不能诱导杀伤相关分子TRAIL及CD107a/b的表达,IL-23可以诱导低水平的pSTAT4但高水平的pSTAT3的表达。     

IL-23/IL-17炎症轴与炎症性肠病的关系研究进展

肠黏膜慢性炎症损伤是炎症性肠病(IBD)的重要病变特点,研究表明白细胞介素23(IL-23)/IL-17炎症轴参与肠黏膜炎性损伤并参与IBD的发生、发展、治疗与转归.IL-23为IL-17重要上游分子,可促进Th17细胞活化、增殖和炎性细胞因子的分泌,并参与IBD病变局部中性粒细胞、单核巨噬细胞、调节性T细胞(Treg...     

SARS患者血清IL-2、IL-10和IL-12的检测

为了探讨细胞因子与SARS患者感染的关系 ,用ELISA的方法对急性期、恢复期SARS患者、慢性乙肝患者和正常人血清进行了IL 2、IL 10和IL 12水平检测 ,并对 14例急性期和恢复期SARS患者的白介素水平变化进行了配对分析。结果显示 :急性期SARS患者的IL 2、IL 10、IL 12水平显著高于恢复期患者及慢性乙肝患者和健康人的水平 (P <0 0 5 )。提示 :细胞因子在SARS感染中可能起重要作用。     

变应性鼻炎患者血清IL-17和IL-23的表达及临床意义

目的:检测变应性鼻炎(Allergic rhinitis,AR)患者血清IL-17和IL-23的表达水平并探讨其临床意义。方法:检测25例AR患者(观察组)血清IL-17、IL-23、s Ig E(过敏原特异性Ig E)的表达水平,并以23名健康体检合格者(对照组)为对照,比较两组人群血清中IL-17、IL-23、s Ig E表达水平的差异,并探讨AR患者血清中IL-17、IL-23、s Ig E三者间的相互关系。结果:观察组患者血清中IL-17、IL-23及s Ig E水平均高于对照组(P均0.01);观察组患者血清中IL-17、IL-23、s Ig E三者两两之间均呈线性正相关关系(P均0.05)。结论:IL-17、IL-23参与了AR的发生发展过程,与s Ig E的形成可能有关。     

人白细胞介素家族的新成员——IL-19、IL-20、IL-21、IL-22、IL-23

白细胞介素是激活的 T细胞分泌的一类细胞因子 ,它们在免疫调节中发挥重要作用 ,具有很高的临床应用价值。迄今为止 ,已有 2 3种人白细胞介素被发现 ,构成了一个庞大的家族。其中 2 0 0 0～ 2 0 0 1年间 ,就有 5种人白细胞介素家族最新成员的序列被阐明。本文简单介绍了它们的结构、诱导表达方式、功能、及其信号相关受体等各个方面的最新研究进展     

脂多糖和金黄色葡萄球菌对IL-23、IL-12表达的调控

目的：检测脂多糖（LPS）和金黄色葡萄球菌（SAC）对人外周血单个核细胞（PBMC）IL-23和IL-12各亚基表达的调节作用并探索其作用机制。方法：用LPS和SAC直接刺激人PBMC，或用CD14抗体或p38丝裂原活化蛋白激酶（MAPK）抑制剂Mastoparan预处理PBMC后再予LPS和SAC刺激，半定量RT-PCR方法检测IL-23p19、IL-12p35和IL-12p40亚基的基因表达变化。结果：人PBMC组成性表达p19和p35，不表达p40。LPS和SAC可上调各亚基的表达。LPS诱导的IL-23和IL-12各亚基表达均需通过CDl4；CDl4仅部分参与SAC诱导的IL-12p40和p35表达上调，而与p19上调无关。LPS和SAC诱导的IL-23和IL-12各亚基表达均需要p38MAPK通路。结论：LPS和SAC刺激下IL-23和IL-12亚基表达及信号传导通路既有相似之处又有不同点，为单独或同时调控这两种因子的表达提供线索。     

白介素-12及白介素-23对胃癌组织中CD4^＋记忆T细胞的影响

目的:探讨胃癌组织中IL-12、IL-23对CD4+记忆T细胞(CD4+Tm)的影响.方法:ELISA检测TNM不同期胃癌组织匀浆中IL-12、IL-23含量;不连续密度梯度离心法分离胃癌组织中的肿瘤浸润淋巴细胞(TIL),流式细胞仪检测TIL中CD4+ Tm及其亚群TEM和TCM在不同期胃癌组织中的分布状况.结果:TNM-Ⅰ、Ⅱ期胃癌组织中IL-12含量差别不明显,但均显著高于TNM-Ⅲ、TNM-Ⅳ期;TNM-Ⅰ期胃癌组织中IL-23的含量高于TNM-Ⅱ、TNM-Ⅲ、TNM-Ⅳ期.胃癌TIL中CD4+ Tm及TEM比例随TNM分期增加逐渐降低,而TCM比例逐渐升高.结论:胃癌组织中IL-12、IL-23含量的变化与胃癌TNM分期有关,且影响胃癌TIL中CD4+记忆T细胞及其亚群TCM和TEM的分布.     

Ovarian follicular concentration of IL-12, IL-15, IL-18 and p40 subunit of IL-12 and IL-23

BACKGROUND: The aim of the study was to determine the presence of interleukin (IL)-12, IL-15, IL-18 and p40 subunit of IL-12/IL-23 in follicular fluid from spontaneous cycles and the relation between the concentration of selected cytokines and IVF-embryo transfer outcome. METHODS: IVF-embryo transfer and enzyme immunoassay (EIA) (R&D Systems, Minneapolis, MN, USA and MBL, Nagoya, Japan) were used. RESULTS: Follicular fluid of women included in the IVF-embryo transfer procedure contained common p40 subunit of IL-12/IL-23 (median 70.1 pg/ml), IL-15 (median 1.3 pg/ml) and IL-18 (median 38.2 pg/ml). There was a significant negative correlation between follicular fluid concentrations of IL-15 and IL-18 (R=-0.392, P=0.003). Significantly higher concentrations of common p40 subunit of IL-12/IL-23 (median 79.8 pg/ml) were found in the follicular fluid taken from follicles containing oocytes, when compared with those without an oocyte (median 44.5 pg/ml, P=0.006). Patients who achieved clinical pregnancy had significantly decreased concentration of IL-15 (median 0.8 pg/ml) compared with patients without successful IVF-embryo transfer outcome (median 1.4 pg/ml, P=0.047). CONCLUSION: Follicular fluid collected from spontaneous cycles contains detectable levels of p40 subunit of IL-12/IL-23, IL-15 and IL-18. Increased concentrations of p40 subunit of IL-12/IL-23 in follicles containing oocytes suggest an important role of this cytokine in reproduction. Possible negative value of IL-15 as a predictor of IVF-embryo transfer success remains to be determined.     

Potential role for IL-23 in hepatic ischemia/reperfusion injury

Summary. IL-12 and IL-23 are related cytokines that share a p40 subunit. Our previous studies identified IL-12 as a primary initiator of the cytokine cascade induced after hepatic ischemia/reperfusion. Because those studies were conducted prior to the discovery of IL-23, it is not clear whether IL-12 or IL-23 is the relevant cytokine in this response. The current studies show that the antibodies used in our original study cross-react with IL-23. We also found that both IL-12 p35 and IL-23 p19 mRNA are expressed rapidly in the liver after ischemia/reperfusion. Finally, isolated Kupffer cells produced TNFα in response to IL-23, but not IL-12, suggesting that IL-23 may be the relevant initiator of the hepatic inflammatory response to ischemia/reperfusion. Received 19 August 2005; returned for revision 5 December 2005; accepted by K. Visvanathan 27 January 2006     

Sphingosine-1-phosphate differently regulates the cytokine production of IL-12, IL-23 and IL-27 in activated murine bone marrow derived dendritic cells

Sphingosine-1-phosphate (S1P) modulates many cell functions such as lymphocyte trafficking and signaling as well as keratinocyte proliferation. However, less is known about the specific effects of S1P on cytokine production, particularly on the interaction between dendritic cells (DCs) and keratinocytes, cell types which are crucial for the initiation and maintenance of chronic inflammatory skin diseases like atopic dermatitis or psoriasis. Especially the cytokines of the IL-12 family play a dominant role in many inflammatory diseases as they have a significant impact on T-helper cell function. In the present study we show that S1P decreased the production of the pro-inflammatory cytokines IL-12 and IL-23 in LPS-stimulated DCs via the common subunit p40 as well as in the crosstalk with activated keratinocytes. By using specific S1P receptor agonists (SEW2871, FTY720-P) and antagonist (JTE013) we identified an important role for S1P receptor 1 in the modulation of the cytokine profile. While diminishing IL-12 and IL-23 secretion, S1P enhanced IL-27 production in DCs. To elucidate the mechanism of the different impact on the IL-12 family cytokine production, we investigated the mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K) pathways in DCs. By using specific MAPK-Inhibitors (U0126, SB202190, SP600125) we demonstrated that ERK, p38 and JNK differently regulate each pathway of each cytokine. While p38 and JNK did not seem to play a role in the modulation properties of S1P on cytokine production, ERK is at least partially involved in the S1P mediated modulation of IL-12 and IL-27. The PI3K-Inhibitor abrogated the S1P-induced decrease of IL-12 and IL-23 secretion, while it had no influence on the S1P-induced increase of IL-27 production. These data implicate, that S1P has an anti-inflammatory impact on the production of IL-12 family cytokines, indicating therapeutic potential for S1P treatment of several inflammatory diseases like psoriasis.     

Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity

IL-23-dependent IL-17-producing T helper (Th) lymphocytes are associated with autoimmunity. We investigated the immunopathological mechanisms for activation of Th17 cells of patients with systemic lupus erythematosus (SLE). Concentration of cytokines/chemokine in plasma and culture supernatant from SLE patients and healthy controls were measured by ELISA or flow cytometry. Plasma IL-12, IL-17, IL-23 and CXCL10 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects (both p < 0.05). Elevated IL-12, IL-17 and CXCL10 concentrations correlated positively and significantly with SLEDAI (all p < 0.05). Plasma IL-12 and IL-17 showed significant and positive correlation with plasma Th1 chemokine CXCL10 concentration in SLE patients (all p < 0.05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p < 0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE.     

IL-23/IL-17轴在银屑病免疫发病机制中的作用

银屑病是一种以T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。Th17细胞及IL-23/IL-17轴在银屑病的发病机制中可能处于关键地位,并成为新的治疗靶标。IL-23诱导Th17细胞分化增殖,分化成熟的Th17可以分泌IL-17、IL-21、IL-22等多种细胞因子,Th17类细胞因子在银屑病等多种自身免疫疾病和炎性疾病中起重要作用。