Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease
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DOI：
10.1002/ibd.20342
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发表时间：
2008-04-01
影响因子：
4.9
通讯作者：
Denson, Lee A.
中科院分区：
文献类型：
--
作者：
Carey, Rebecca;Jurickova, Ingrid;Denson, Lee A.
背景资料：虽然IL-6依赖性转录因子信号转导子和转录激活子3（STAT 3）的激活与炎症性肠病（IBD）的发病机制有关，但尚未显示对粘膜基因表达和炎症的直接影响。我们假设，促炎性IL 6：STAT 3依赖的生物网络将上调在儿科发病的IBD patients，并将与粘膜inflammation.Methods的严重程度：儿科发病的IBD患者在诊断和治疗过程中被招募。使用Bioplex进行血清细胞因子分析。通过流式细胞术评估外周血白细胞（PBL）中的STAT 3磷酸化（pSTAT 3）。采用免疫组织化学方法对pSTAT 3和STAT 3靶基因进行定位。微阵列分析被用来确定RNA表达谱从结肠biopsies.Results：循环IL-6上调活动性IBD患者在诊断和治疗过程中。在IBD患者的PB C粒细胞、IL-6刺激的CD 3（+）/CD 4（+）淋巴细胞和受影响的结肠活检组织中，STAT 3活化增加。pSTAT 3 + PB粒细胞和结肠上皮及固有层细胞的频率与粘膜炎症程度高度相关。微阵列和免疫系统生物信息学分析确定IL-6：STAT 3依赖的生物网络上调IBD患者控制白细胞募集，HLA表达，血管生成，和tissue remodeling.Conclusions：一个促炎性IL-6：STAT 3生物网络是上调活跃的小儿IBD患者在诊断和治疗过程中。该网络的特异性靶向可能在C减少粘膜炎症中有效。
Background: While activation of the IL-6-dependent transcription factor signal transducer and activator of transcription 3 (STAT3) has been implicated in the pathogenesis of inflammatory bowel disease (IBD), a direct effect on mucosal gene expression and inflammation has not been shown. We hypothesized that a proinflammatory IL6:STAT3-dependent biological network would be up regulated in pediatric-onset IBD patients, and would be associated with the severity of mucosal inflammation.Methods: Patients with pediatric-onset IBD were enrolled at diagnosis and during therapy. Serum cytokine analysis was performed using Bioplex. STAT3 phosphorylation (pSTAT3) in peripheral blood leukocytes (PBLs) was assessed by flow cytometry. Immunohistochemistry of colonic mucosa was used to localize pSTAT3 and STAT3 target genes. Microarray analysis was used to determine RNA expression profiles from colon biopsies.Results: Circulating IL-6 was upregulated in active IBD patients at dia2nosis and during therapy. STAT3 activation was increased in PB C granulocytes, IL-6-stimulated CD3(+)/CD4(+) lymphocytes, and affected colon biopsies of IBD patients. The frequency of pSTAT3+ PB granulocytes and colon epithelial and lamina propria cells was highly correlated with the degree of mucosal inflammation. Microarray and Ingenuity Systems bioinformatics analysis identified IL-6: STAT3-dependent biological networks upregulated in IBD patients which control leukocyte recruitment, HLA expression, angiogenesis, and tissue remodeling.Conclusions: A proinflammatory IL6:STAT3 biologic network is upregulated in active pediatric IBD patients at diagnosis and during therapy. Specific targeting of this network may be effective in C reducing mucosal inflammation.