Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement
Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement
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DOI：
10.1016/j.cyto.2018.11.013
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发表时间：
2019-05-01
期刊：
影响因子：
3.8
通讯作者：
Mueller-Ladner, Ulf
中科院分区：
文献类型：
--
作者：
Neumann, Elena;Lepper, Nina;Mueller-Ladner, Ulf
目的：脂肪因子的免疫调节特性在自身免疫性疾病中已有报道。关于脂肪因子在系统性硬化症（SSc）中的作用知之甚少。肺和胃肠道是经常参与SSc，因此，这些器官的脂肪因子的表达进行了分析，以及患有特发性肺纤维化（IPF）作为comparation.Methods：胃样本（胃窦，体）的SSc进行了化学分析脂联素，内脂素和visfatin相比，非SSc相关胃炎。在胃样品中定量炎性细胞并与脂肪因子表达相关。还分析了SSc、IPF和健康对照的肺样本。结果：供体肺实质切片显示出与IPF和SSc相比明显更强的脂联素信号（供体与IPF：p < 0.0001）。在SSc和IPF中，在免疫细胞浸润中，lgn和内脂素增加，但与对照组相比，lgn或内脂素的表达总体上没有差异。在纤维化早期的BAL和肺蛋白裂解物中，与对照组相比，IPF和SSc中的脂联素和内脂素未降低。在通过标准内镜胃活检收集的胃样本中，与非SSc胃炎相比，SSc胃炎中的脂联素也显著降低（p = 0.049），而尽管相应样本中不包括更深的纤维化层，但脂联素和内脂素相当。脂联素阳性组织中CD4（+）T细胞数量较多，而CD8（+）T细胞数量较少。对照组显示CD4（+）T细胞和CD4 + T细胞之间无相关性，而SSc组显示抵抗素阴性组织中CD4（+）T细胞显著增多。结论：脂肪因子在SSc患者的胃和肺样本中表达，在IPF患者的肺样本中也表达。显著地，脂联素水平在纤维化SSc胃炎组织以及IPF和SSc肺组织中降低。因此，脂联素表达似乎与SSc和IPF背景下的纤维化进展相关。
Objectives: The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison.Methods: Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA.Results: Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc-compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4(+) but not CD8(+) T cells. Controls showed no correlation between CD4(+) T cells and resistin, whereas SSc showed significantly more CD4(+) T cells in resistin-negative tissues.Conclusion: Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF.