Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: macrophage harbingers of disease severity.
Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: macrophage harbingers of disease severity.
复制标题
DOI：
10.1002/art.30465
复制
发表时间：
2011-10
影响因子：
--
通讯作者：
Wahl, Sharon M.
中科院分区：
文献类型：
--
作者：
Greenwell-Wild, Teresa;Moutsopoulos, Niki M.;Gliozzi, Maria;Kapsogeorgou, Efstathia;Rangel, Zoila;Munson, Peter J.;Moutsopoulos, Haralampos M.;Wahl, Sharon M.
干燥综合征（SS）是一种病因不明的慢性自身免疫性疾病，以唾液腺和泪腺为靶点，可伴有多器官系统表现。为了进一步了解与SS相关的免疫病理学并揭示治疗靶点，我们比较了患有严重炎症的唾液腺与轻度或无疾病的唾液腺的基因表达谱。我们使用SS患者和对照组唾液腺组织的微阵列分析，通过真实的时间PCR和蛋白质分析确定了在组织、血清和培养细胞群中进一步表征的靶基因。其中最高表达的SS基因与髓系细胞，包括哺乳动物几丁质酶家族的成员，以前没有与外分泌蛋白病相关的基因。几丁质酶-3-like-1（CHI 3L 1/YKL-40）和几丁质酶1（CHIT 1），高度保守的几丁质酶样糖蛋白，一种具有酶活性，一种缺乏酶活性，在转录组水平是明显的，并且在发炎组织中检测到。几丁质酶在单核细胞向巨噬细胞分化过程中表达，并通过细胞因子（包括IFNα）增强。由于这些和其他巨噬细胞衍生分子的表达升高与更严重的SS相对应，这些观察结果表明潜在的免疫病理巨噬细胞参与，此外，组织巨噬细胞转录谱反映了IFNα诱导的多个基因。
Sjögren’s syndrome(SS) represents a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multi-organ systemic manifestations. To further an understanding of immunopathology associated with SS and uncover therapeutic targets, we compared gene expression profiles of salivary glands with severe inflammation to those with mild or no disease. Using microarray profiling of salivary gland tissues from SS patients and controls, we identified target genes that were further characterized in tissues, serum and in cultured cell populations by real time PCR and protein analyses. Among the most highly expressed SS genes were genes associated with myeloid cells, including members of the mammalian chitinase family, not previously associated with exocrinopathies. Both chitinase-3-like-1(CHI3L1/YKL-40) and chitinase 1(CHIT1), highly conserved chitinase-like glycoproteins, one with and one lacking enzymatic activity, were evident at the transcriptome level, and detected within inflamed tissues. Chitinases are expressed during monocyte-to-macrophage differentiation, and augmented by cytokines, including IFNα. Since elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, these observations suggest potential immunopathologic macrophage involvement and furthermore, that the tissue macrophage transcriptional profile reflects multiple genes induced by IFNα.
登录
查看更多内容
影响因子：
--
作者：
Hu, Shen;Zhou, Michael;Jiang, Jiang;Wang, Jianghua;Elashoff, David;Gorr, Sven;Michie, Sara A.;Spijkervet, Fred K. L.;Bootsma, Hendrika;Kallenberg, Cees G. M.;Vissink, Arjan;Horvath, Steve;Wong, David T.
通讯作者：
Wong, David T.
DOI：
10.4049/jimmunol.182.1.34
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kariuki SN;Kirou KA;MacDermott EJ;Barillas-Arias L;Crow MK;Niewold TB
通讯作者：
Niewold TB
影响因子：
1.6
作者：
Guan, Shou-Ping;Mok, Yu-Keung;Wong, W. S. Fred
通讯作者：
Wong, W. S. Fred
影响因子：
4.4
作者：
Mathur, Anubhav N.;Chang, Hua-Chen;Kaplan, Mark H.
通讯作者：
Kaplan, Mark H.
影响因子：
6
作者：
Katsifis, Gikas E.;Rekka, Sofia;Wahl, Sharon M.
通讯作者：
Wahl, Sharon M.