TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.
TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.
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DOI：
10.1111/j.1582-4934.2011.01456.x
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发表时间：
2012-08
影响因子：
5.3
通讯作者：
Azuma M
中科院分区：
文献类型：
--
作者：
Yamamura Y;Motegi K;Kani K;Takano H;Momota Y;Aota K;Yamanoi T;Azuma M
干燥综合征是一种以唾液和泪液分泌减少为特征的全身性自身免疫性疾病。这些减排背后的机制仍不清楚。我们先前已经证明，肿瘤坏死因子-α在腺泡结构的破坏中起着重要作用。在此，我们检测了肿瘤坏死因子-α的S在人涎腺腺泡细胞水通道蛋白5表达中的作用。用肿瘤坏死因子-α处理永生化的人涎腺腺泡细胞(NS-SV-AC)，分析AQP5mRNA和蛋白的表达水平。此外，还探讨了肿瘤坏死因子-α降低AQP5表达的机制。用肿瘤坏死因子-α处理NS-SV-AC细胞后，AQP5mRNA和蛋白的表达水平显著降低，净液体分泌率降低。我们检测了经肿瘤坏死因子-α处理的NS-SV-AC细胞中DNA甲基转移酶(DNMT)的表达和激活水平。而Dnmt1、DNMT3a和Dnmt3b的表达或激活水平无明显变化。虽然我们还研究了核因子-κB活性在肿瘤坏死因子-α诱导的抑制NS-SV-AC细胞AQP5表达中的作用，但我们在未转染的细胞和I-αB-κ的超阻遏子形式的细胞克隆中发现了类似的肿瘤坏死因子-α对水通道蛋白5表达的抑制。然而，有趣的是，染色质免疫沉淀分析显示，在NS-SV-AC细胞中，经肿瘤坏死因子-α处理后，与AQP5基因启动子相关的乙酰化组蛋白H4水平显著降低。因此，我们的结果可能表明，肿瘤坏死因子-α抑制人唾液腺腺泡细胞AQP5的表达可能是由于抑制组蛋白H4乙酰化的表观遗传学机制。
Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.
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