Melatonin Modulates ZAP70 and CD40 Transcripts via Histone Modifications in Canine Ileum Epithelial Cells.

IF 2 2区 农林科学 Q2 VETERINARY SCIENCES
Jian Hong, Saber Y Adam, Shiqi Wang, Hao Huang, In Ho Kim, Abdelkareem A Ahmed, Hao-Yu Liu, Demin Cai
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Abstract

Melatonin (MLT), produced by the pineal gland and other tissues, is known for its anti-inflammatory effects, particularly in regulating inflammatory markers and cytokines in intestinal cells. Our study aimed to investigate how MLT influences the expression of inflammatory genes through histone modification in canine ileum epithelial cells (cIECs). In our experiment, cIECs were cultured and divided into a control group (CON) and an MLT-treatment group. MLT did not significantly affect cell growth or death in cIECs compared to the CON. However, MLT treatment led to an upregulation of CD40, ZAP70, and IL7R and a downregulation of LCK, RPL37, TNFRSF13B, CD4, CD40LG, BLNK, and CIITA at the mRNA expression level. Moreover, MLT significantly altered the NF-kappa B signaling pathway by upregulating genes, such as CD40, ZAP70, TICAM1, VCAMI, GADD45B, IRAK1, TRADD, RELA, RIPK1, and RELB, and downregulating PRKCB, LY96, CD40LG, ILIB, BLNK, and TNFRSF11A. Using ChIP-qPCR, we discovered that MLT treatment enhanced histone acetylation marks H3K9ac, H3K18ac, H3K27ac, and methylation marks H3K4me1 and H3K4me3 at the ZAP70 and CD40 gene loci (p < 0.05). Additionally, the enrichment of RNA polymerase II and phosphorylated Ser5 pol-II at these loci was increased in MLT-treated cells (p < 0.05), indicating heightened transcriptional activity. In conclusion, our findings suggest that MLT mitigates inflammation in cIECs by modulating the transcription of ZAP70 and CD40 through histone modifications, offering potential therapeutic insights for inflammatory bowel diseases.

褪黑素通过组蛋白修饰调节犬回肠上皮细胞的ZAP70和CD40转录本。
褪黑素(MLT)由松果体和其他组织产生,以其抗炎作用而闻名,特别是在调节肠细胞中的炎症标志物和细胞因子方面。本研究旨在探讨MLT如何通过组蛋白修饰影响犬回肠上皮细胞(cIECs)炎症基因的表达。在我们的实验中,cIECs被培养并分为对照组(CON)和mlt处理组。与对照组相比,MLT对cIECs细胞生长或死亡没有显著影响。然而,MLT治疗导致CD40、ZAP70和IL7R上调,LCK、RPL37、TNFRSF13B、CD4、CD40LG、BLNK和CIITA mRNA表达水平下调。此外,MLT通过上调CD40、ZAP70、TICAM1、VCAMI、GADD45B、IRAK1、TRADD、RELA、RIPK1、RELB等基因,下调PRKCB、LY96、CD40LG、ILIB、BLNK、TNFRSF11A等基因,显著改变NF-kappa B信号通路。通过ChIP-qPCR,我们发现MLT处理增强了ZAP70和CD40基因位点上的组蛋白乙酰化标记H3K9ac、H3K18ac、H3K27ac以及甲基化标记H3K4me1和H3K4me3 (p < 0.05)。此外,这些位点上RNA聚合酶II和磷酸化Ser5 pol-II的富集在mlt处理的细胞中增加(p < 0.05),表明转录活性增强。总之,我们的研究结果表明,MLT通过组蛋白修饰调节ZAP70和CD40的转录来减轻ciec中的炎症,为炎症性肠病的治疗提供了潜在的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Veterinary Sciences
Veterinary Sciences VETERINARY SCIENCES-
CiteScore
2.90
自引率
8.30%
发文量
612
审稿时长
6 weeks
期刊介绍: Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.
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