Gomes Renan Garcia, Brito Carlos Alexandre Antunes de, Martinelli Valéria Ferreira, Santos Rossana Nascimento Dos, Gomes Fabiana Oliveira Dos Santos, Peixoto Christina Alves, Crispim Janaína Oliveira, Diniz George Tadeu Nunes, Donadi Eduardo Antônio, Lucena-Silva Norma
Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.
Department of Internal Medicine, School of Medicine, Federal University of Pernambuco, Recife, Brazil.
Hum Immunol. 2018 Jun;79(6):477-484. doi: 10.1016/j.humimm.2018.03.006. Epub 2018 Mar 26.
HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.
HLA - G是一种可由上皮细胞产生的免疫调节分子。鉴于肿瘤坏死因子（TNF）和白细胞介素 - 10（IL - 10）参与肠道炎症性疾病，且这两种细胞因子均可调节HLA - G，我们通过定量聚合酶链反应（qPCR）评估了HLA - G、TNF和IL - 10的信使核糖核酸（mRNA）表达，并通过免疫组织化学检测了一名患有克罗恩病（CD）或溃疡性结肠炎（UC）患者的两份呈现不同炎症程度的肠道样本中的HLA - G蛋白水平。与低炎症区域相比，在呈现强烈炎症的肠道区域中，组织HLA - G5（P < 0.0001）、TNF（P = 0.0004）和IL - 10（P = 0.0169）的mRNA表达水平更高，且HLA - G蛋白水平与黏膜炎症程度无关。在CD中，低炎症区域TNF的表达与IL - 10相关，TNF与IL - 10的比值为3，但在炎症区域该比值增至9倍。在UC中，无论炎症分级如何，TNF的表达均与IL - 10相关，不同炎症区域的TNF与IL - 10比值变化不大。在轻度炎症区域，TNF和IL - 10的表达与HLA - G5的表达相关。CD和UC样本均呈现HLA - G的基因和蛋白表达；且根据潜在炎症性肠病的类型，HLA - G5的表达与TNF和IL - 10水平的相关性存在差异。
