Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation.
Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation.
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DOI：
10.1002/ibd.21306
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发表时间：
2010-11
影响因子：
4.9
通讯作者：
Brand, Stephan
中科院分区：
文献类型：
--
作者：
Diegelmann, Julia;Seiderer, Julia;Niess, Jan-Hendrik;Haller, Dirk;Goeke, Burkhard;Reinecker, Hans-Christian;Brand, Stephan
关键词：
CXCL16介导革兰氏阴性和革兰氏阳性细菌的黏附和吞噬，对CXCR6+T细胞具有很强的趋化作用。在本研究中，我们确定了迄今为止未知的CXCL16-CXCR6趋化因子-配体受体系统在体内和体外肠道炎症中的表达和信号转导。用定量聚合酶链式反应方法检测了克罗恩病(CD)患者的结肠活检组织、Δ小鼠回肠炎模型和小鼠巨细胞病毒(MCMV)诱导的结肠炎组织中CXCL16mRNA的表达。采用双抗体夹心法检测血清CXCL16水平。用磷酸化MAP激酶和Akt抗体分析CXCL16诱导的IEC信号转导。我们发现CXCL16和CXCR6的表达模式相反，CXCL16在近端小鼠小肠中的表达水平最高，而CXCR6在远端结肠中的表达水平最高。CXCL16和CXCR6在结直肠癌来源的IEC细胞中表达。CXCL16诱导的MAPK和Akt激活表明，CRC表达的CXCR6具有功能。在肿瘤坏死因子Δ小鼠回肠炎模型和巨细胞病毒诱导的结肠炎模型(p<；0.05)和CD患者的血清和结肠(p<；0.05)中，CXCL16的表达均升高，其表达与CXCR6和IL-8水平高度相关(r分别为0.85和0.89)。CRC来源的IEC表达功能性CXCL16受体CXCR6。CXCL16mRNA和蛋白在体外和CD患者的肠炎症中表达上调，提示这种趋化因子在肠炎症中起重要作用。
CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16-CXCR6 chemokine-ligand receptor system in intestinal inflammation in vivo and in vitro. CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn’s disease (CD) as well as in the TNFΔARE mouse model of ileitis and in murine cytomegalovirus (MCMV)-induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in IEC with phospho-specific antibodies for MAP kinases and Akt. We found an inverse expression pattern of CXCL16 and CXCR6 with highest CXCL16 mRNA levels in the proximal murine small intestine and highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC)-derived IEC lines. CRC-expressed CXCR6 was functional as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNFΔARE mouse model of ileitis and in MCMV-induced colitis (p<0.05) and in the sera and colons of patients with CD (p<0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r=0.85 and 0.89, respectively). CRC-derived IEC express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation.
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影响因子：
32.4
作者：
Kontoyiannis, D;Pasparakis, M;Kollias, G
通讯作者：
Kollias, G
影响因子：
29.4
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作者：
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Lohse, P