共查询到20条相似文献,搜索用时 0 毫秒
1.
2.
3.
Caruso R Fina D Paoluzi OA Del Vecchio Blanco G Stolfi C Rizzo A Caprioli F Sarra M Andrei F Fantini MC MacDonald TT Pallone F Monteleone G 《European journal of immunology》2008,38(2):470-478
Helicobacter pylori (Hp) infection is associated with a marked infiltration of the gastric mucosa by inflammatory cells. The molecular pathways that control Hp-associated inflammatory reaction are complex, but locally induced cytokines seem to contribute to maintaining the ongoing inflammation. We have previously shown that IL-17 is over-produced in Hp-infected gastric mucosa, and that IL-17 stimulates the synthesis of IL-8, the major neutrophil chemoattractant. Factors/mechanisms that regulate IL-17 expression remain, however, unknown. In this study, we initially expanded our previous data, showing that CD4(+) and CD8(+) T cells are a source of IL-17 in Hp-infected samples. Since IL-23 enhances T cell-derived IL-17 during bacterial infections, we then assessed the role of IL-23 in controlling IL-17 expression in Hp-colonized stomach. Using real-time PCR and ELISA, IL-23 was detected in all gastric biopsies, but its expression was more pronounced in Hp-infected samples in comparison to controls. Treatment of normal gastric lamina propria mononuclear cells (LPMC) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of Stat3 prevented IL-23-driven IL-17 synthesis. Consistently, blockade of IL-23 in cultures of LPMC from Hp-infected patients reduced Stat3 activation and IL-17 production. Data show that IL-23 is overexpressed in Hp-infected gastric mucosa where it could contribute to sustaining IL-17 production. 相似文献
4.
5.
6.
Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression 总被引:1,自引:0,他引:1
Jackson CB Judd LM Menheniott TR Kronborg I Dow C Yeomans ND Boussioutas A Robb L Giraud AS 《The Journal of pathology》2007,213(2):140-151
H. pylori infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal H. pylori pathogenicity-associated CagA protein disrupts intracellular SHP-2 signalling pathways including those used by the IL-6 family cytokines, IL-6 and IL-11. Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known H. pylori and CagA status, we investigated whether (i) STAT3 and ERK1/2 activation is altered in H. pylori-dependent gastritis; (ii) these profiles are more pronounced in CagA+ H. pylori infection; and (iii) the expression of pro-inflammatory cytokines that activate STAT3 and ERK 1/2 pathways is associated with progression to gastric cancer. IL-6, IL-11, and activated STAT3 and ERK1/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1/2 activation (p = 0.001) in H. pylori-dependent gastritis, which was further enhanced in the presence of CagA+ H. pylori strains. Of known gastric ligands that drive STAT3 activation, IL-6 expression was increased after H. pylori infection and both IL-6 and IL-11 were strongly up-regulated in the gastric cancer biopsies. This suggests a mechanism by which IL-11 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an in vitro approach, demonstrating that recombinant human IL-11 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1/2 activation in H. pylori-dependent gastritis that is likely driven in an IL-6-dependent fashion. IL-11 expression is associated with adenocarcinoma development, but not gastritic lesions, and we identify a novel mechanism for IL-11 as a potent inducer of proliferation in the human gastric cancer setting. 相似文献
8.
Mice with defective IL-17 immunity display a broad vulnerability to various infectious agents at diverse mucocutaneous surfaces. In humans, the study of patients with various primary immunodeficiencies, including autosomal dominant hyper-IgE syndrome caused by dominant-negative STAT3 mutations and autosomal recessive autoimmune polyendocrinopathy syndrome type 1 caused by null mutations in AIRE, has suggested that IL-17A, IL-17F and/or IL-22 are essential for mucocutaneous immunity to Candida albicans. This hypothesis was confirmed by the identification of rare patients with chronic mucocutaneous candidiasis (CMC) due to autosomal recessive IL-17RA deficiency and autosomal dominant IL-17F deficiency. Heterozygosity for gain-of-function mutations in STAT1 in additional patients with CMC was recently shown to inhibit the development of IL-17 T cells. Although the infectious phenotype of patients with CMC and inborn errors of IL-17 immunity remains to be finely delineated, it appears that human IL-17A and IL-17F display redundancy for protective immunity in natural conditions that is not seen in their mouse orthologs in experimental conditions. 相似文献
9.
Pignatti P Ciapponi L Galle P Hansen MB Massa M Meazza C Paonessa G Novick D Ciliberto G Martini A De Benedetti F 《Clinical and experimental immunology》2003,131(2):355-363
We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6. 相似文献
10.
Yang Liu Jian Zhang Yu-Hui Zhou Yi-Na Jiang Wei Zhang Xiao-Jiang Tang Yu Ren Shui-Ping Han Pei-Jun Liu Jing Xu Jian-Jun He 《International journal of clinical and experimental pathology》2015,8(10):12541-12548
Plasma cell mastitis (PCM), a particular type of mastitis, mainly occurs in females at nonpregnant and nonlactating stages. The infiltration of abundant plasma cells and lymphocytes is the hallmark of the disease. The incidence rate of PCM increased gradually and its pathogenesis remained unclear. In this study, we investigated the expression of IL-6/STAT3 signaling pathway, which is vital not only for the differentiation of plasma cells but also for survival of plasma cells and T lymphocytes, in 30 PCM cases, 10 acute mastitis cases and 10 normal breast tissues by immunohistochemical analysis. IL-6 level was significantly higher in PCM patients than in acute mastitis patients or normal group. The positive rate of IL-6 and p-STAT3 staining in PCM samples was 93.3% (28/30) and 70% (21/30), respectively, and there was a significant positive association between IL-6 and p-STAT3 staining (r=0.408, P=0.025). In PCM group, the rate of nipple retraction was 40% (12/30). Significantly higher IL-6 expression was found in PCM patients with nipple retraction than in other PCM patients. However, no significant difference in IL-6 or p-STAT3 staining was detected between PCM patients experiencing recurrence and other PCM patients. In addition, Bcl-2 level was higher in PCM patients than in acute mastitis patients or normal group, but there was no difference in Bcl-2 immunostaining between PCM patients experiencing recurrence and other PCM patients. These indicate that IL-6/STAT3 signaling is activated in PCM and may play an important role in the pathogenesis of PCM. 相似文献
11.
Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate 总被引:1,自引:0,他引:1
Royuela M Ricote M Parsons MS García-Tuñón I Paniagua R de Miguel MP 《The Journal of pathology》2004,202(1):41-49
Interleukin-6 (IL-6) and its receptor have been implicated in prostate cancer progression. Because other members of the IL-6 family such as leukaemia inhibitory factor (LIF) and oncostatin M (OSM) share gp130, the signal transduction subunit of their receptors, interpretation of the data without considering the expression of these cytokines and their specific receptor subunits could be misleading. The immunohistochemical pattern of the IL-6 family and their receptor subunits in normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PC) was investigated. In normal prostates, gp130 and OSMRalpha were detected exclusively in the stroma and LIFRbeta was very scarce. While IL-6 was scarcely immunolocalized to the basal cells of the epithelium, OSM was detected in the stroma and LIF in both the epithelium and the stroma. This suggests an autocrine role for this family of cytokines in the stroma of normal prostates. In BPH, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, whereas LIFRbeta was localized only to the epithelium. IL-6 localized preferentially to the epithelium, OSM to the stroma, and LIF to both compartments. Therefore, in addition to the autocrine role in the stroma, IL-6 and OSM may play a paracrine role from the stroma to the epithelium in BPH. In PC, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, increasing with rising Gleason grade, whereas LIFRbeta was localized exclusively to the epithelium of low Gleason grade carcinomas. IL-6, LIF, and OSM localized in all cell types, with immunostaining increasing with Gleason grade. These data suggest an autocrine role for these cytokines in the epithelial cells of PC. The distinct pattern of expression of LIFRbeta exclusively in low Gleason grade carcinomas makes LIFRbeta a candidate for malignancy diagnosis. The role of OSM mainly in high Gleason grade carcinomas makes OSM a putative target for prostate cancer therapy. 相似文献
12.
目的 探讨IL-6在U937细胞中产生生物学效应的信号转导基础。方法 检测IL-6对U937细胞生长与分化的影响。并采用凝胶阻滞电泳法,检测IL-6在U937细胞中激活核因子的情况。结果 IL-6可诱导U937细胞向巨噬细胞方向分化。分化的细胞酸性醋酸酯酶(ANAE)活性、硝基蓝四唑(NBT)还原能力及CD54表达增强,STAT3可被IL-6显著激活,其活性呈一定的剂量与时间依赖性;而NF-IL6、NF-kB、AP-1及其它STAT家族成员则无明显激活。结论 U937细胞的终分化可能是JAK-STAT3通路介导的。 相似文献
13.
Yu-Xing Jiang Ping-Ang Li Shi-Wei Yang Ying-Xue Hao Pei-Wu Yu 《International journal of clinical and experimental pathology》2015,8(6):7002-7008
Background: Previous researchers have identified that the chemokine interleukin-17 (IL-17) was associated with survival time of patients with gastric cancer, but the roles of its receptors (IL-17R) in gastric cancer remain unknown. Our studies were designed to clarify the function of IL-17RA and to explore their potential role in gastric cancer. Materials and methods: The expression of IL-17RA was determined in primary gastric cancer tissues (n=101) using Real-time RT-PCR, immunohistochemistry, and western blotting. To investigate the functional significance of IL-17RA expression, IL-17RA expression and clinical parameters, multivariate survival was analyzed in patients with gastric cancer. Results: IL-17RA was overexpression in gastric cancer tissues compared with adjacent normal tissues (P<0.05). The elevated expression level of IL-17RA was observed correlated significantly with tumor progression (P=0.003), Lymphatic invasion (P=0.019), lymphoid nodal status (P=0.001), distant metastasis (P<0.001) of gastric cancer patients, TNM stage (P=0.0013) and was one of the independent prognostic factors for patient’s overall survival. Conclusions: These results demonstrated that the expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis of gastric cancer. The IL-17-IL-17RA signaling mechanism may be a potential novel target. 相似文献
14.
目的 :探讨不同反应靶细胞中白细胞介素 6 (IL 6 )对信号转导子与转录激活子 1(STAT1)的激活。方法 :利用抗STAT1和抗酪氨酸磷酸化STAT1的抗体 ,进行免疫印迹分析。结果 :IL 6可促进 7TD1和TF1细胞生长 ,但在这两种细胞中对STAT1的酪氨酸磷酸化水平没有明显影响。M 1、R2和U937细胞在IL 6诱导下生长停止并向巨噬细胞方向分化 ,而IL 6在这 3种细胞中均可激活STAT1,且激活效应有剂量与时间依赖性。结论 :STAT1的活化可能与抑制效应有关。我们的数据有助于解释为什么IL 6在不同效应靶细胞中有不同的生物学效应 相似文献
15.
《Seminars in immunology》2014,26(1):54-74
Inflammatory responses play pivotal roles in cancer development, including tumor initiation, promotion, progression, and metastasis. Cytokines are now recognized as important mediators linking inflammation and cancer, and are therefore potential therapeutic and preventive targets as well as prognostic factors. The interleukin (IL)-6 family of cytokines, especially IL-6 and IL-11, is highly up-regulated in many cancers and considered as one of the most important cytokine families during tumorigenesis and metastasis. This review discusses molecular mechanisms linking the IL-6 cytokine family to solid malignancies and their treatment. 相似文献
16.
17.
Larsen M Arnaud L Hié M Parizot C Dorgham K Shoukry M Kemula M Barete S Derai D Sauce D Amoura Z Pène J Yssel H Gorochov G 《European journal of immunology》2011,41(9):2596-2605
The ontogenic relationship between pro-inflammatory populations of interleukin-17 (IL-17A)- and/or IL-22-producing T cells and other T-cell subsets is currently unclear in humans. To appreciate T helper cell-lineage commitment, we combined cytokine production profiles of in vitro expanded T-cell clones with T-cell receptor (TCR) clonotypic signatures. Moreover, ex vivo cytokine production profiles at the single-cell level were analyzed using an original approach based on the hierarchical cluster analysis of multiparametric flow cytometry data. These combined approaches enabled the delineation of distinct functional T-cell subsets, including Th1, Th2, Tr1, Th17 cells and a highly polyfunctional IL-22-producing T-cell population. Cluster analysis highlighted that the IL-22-producing T-cell population should be considered independently from the Th17 and Th1 subsets, although it was more closely related to the former. In parallel, we observed extensive TCRαβ sharing across all five subsets defined. The strategy described here allows the objective definition of cellular subsets and an unbiased insight into their similarities. Together, our results underscore the ontogenic plasticity of CD4(+) T-cell progenitors, which can adopt a differentiation profile irrespective of antigen specificity. 相似文献
18.
Li-Jun Wu Hai-Xia Li Xiao-Ting Luo Rong-Ze Lu Yun-Fang Ma Rui Wang Jun Zhang Dong-Qin Yang Hua Yu Jie Liu 《International journal of clinical and experimental pathology》2014,7(3):1140-1146
STAT3 is constitutively activated in many human cancers including gastric cancer and plays crucial roles in modulating cancer cell proliferation, survival, metastasis as well as the microenvironment of pre-metastatic niches. Accumulating evidence has implicated STAT3 as a promising target for cancer therapy and it has been well established that tumor cell metastasized to lymph node is associated with poor prognosis. However, little is known about the relation between STAT3 activation in tumor cell-free lymph nodes and patient clinical outcomes. The objective of the current study was to investigate the role of STAT3 activity in tumor cell-free lymph nodes in tumor progression and prognosis for gastric cancer patients. Immunohistochemical analyses for p-STAT3, Ki-67, CD68 and Bcl-xL were performed in tumor cell-free lymph nodes from 60 gastric cancer patients. Survival analysis was conducted by using the Kaplan-Meier method. Immunohistochemical analyses showed that hyperactivity of STAT3 in tumor cell-free lymph nodes was significantly associated with tumor recurrence, and STAT3 activation pattern coincides with expression Ki-67, CD68, Bcl-xL. Survival analysis revealed that persistent STAT3 activation in uninvolved lymph nodes was positively associated with poor overall survival (P<0.05). These findings suggest that STAT3 activation in tumor-free lymph nodes is involved in the pathogenesis and metastasis of gastric cancer and that elevated STAT3 activity in lymph nodes prior to tumor cell arrival may indicate a poorer prognosis. These clinical studies support our findings in mouse tumor models showing that STAT3 activation is crucial for pre-metastatic niche formation and metastasis. 相似文献
19.
The molecular mechanism underlying microRNA (miR)‐17 overexpression has not been clearly evaluated in gastric cancer. We aimed to evaluate the functional roles of miR‐17 in gastric cancer and test its viability as a therapeutic target. We conducted comparative genomic hybridization and expression array analyses on human gastric cancer tissue samples, as well as evaluating the functional roles of miR‐17 in gastric cancer cell lines and transgenic mice. miR‐17 overexpression in gastric cancer patients was associated with copy number gain of proliferation‐associated oncogenes such as MYC, CCNE1, ERBB2, and FGFR2. Copy number gain of MIR17HG gene (13q31.3) was rare, with an overall frequency of 2% in gastric cancers (1 of 51). miR‐17 knockdown suppressed the monolayer and anchorage‐independent growth of FGFR2‐amplified KATO‐III gastric cancer cells. mir‐17–92 TG/TG mice overexpressing the mir‐17–92 cluster under the villin promoter developed spontaneous benign tumors in the intestinal tract (log‐rank P for tumor‐free survival = 0.069). Taken together, miR‐17 overexpression in gastric cancer was rarely associated with MIR17HG gene amplification, but correlated with proliferation‐associated oncogene amplification. Therefore, miR‐17‐targeting approach may benefit patients with gastric cancers harboring proliferation‐associated oncogene amplification. 相似文献