Jan Iqra, Rather Rafiq A, Mushtaq Ifra, Malik Ajaz A, Besina Syed, Baba Abdul Basit, Farooq Muzamil, Yousuf Tahira, Rah Bilal, Afroze Dil
Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India.
Department of Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India.
Front Oncol. 2021 Jan 25;10:604747. doi: 10.3389/fonc.2020.604747. eCollection 2020.
infection has been associated with the onset of gastric mucosal inflammation and is known to perturb the balance between T-regulatory (Treg) and T-helper 17 (Th17) cells which causes a spurt of interleukin 17 (IL17) and transforming growth factor-β (TGF-β) from Th17 and Treg cells within the gastric milieu. IL17 instigates a surge of interleukin 6 (IL6) from T-helper 1 (Th1) and T-helper 2 (Th2) cells. Further, infection is known to stimulate the atypical DNA methylation in gastric mucosa. However, the precise role of cytokine signaling in induction of epigenetic modifications during gastric carcinogenesis is vaguely understood. In this study, patient samples from were examined using real-time polymerase chain reaction (qPCR), PCR, methylation-specific (MS)-PCR, and enzyme-linked immunosorbent assays. We found that infection augments the production of interleukin 10 (IL10), IL6, and TGF-β in the gastric milieu and systemic circulation. Together with the IL6/IL10 mediated hyperactivation of the JAK/STAT pathway, infection causes the inactivation of suppressor of cytokine signaling 1 () gene through the hypermethylation of the promoter region. This study signifies that -mediated epigenetic silencing of in concert with inflammatory cytokines miffs hyperactivation of the JAK/STAT cascade during gastric carcinogenesis.
感染与胃黏膜炎症的发生有关，已知会扰乱调节性T细胞（Treg）和辅助性T细胞17（Th17）之间的平衡，这会导致胃内环境中Th17和Treg细胞释放大量白细胞介素17（IL17）和转化生长因子-β（TGF-β）。IL17会促使辅助性T细胞1（Th1）和辅助性T细胞2（Th2）释放大量白细胞介素6（IL6）。此外，已知感染会刺激胃黏膜中的非典型DNA甲基化。然而，细胞因子信号传导在胃癌发生过程中诱导表观遗传修饰的确切作用尚不清楚。在本研究中，使用实时聚合酶链反应（qPCR）、PCR、甲基化特异性（MS）-PCR和酶联免疫吸附测定法对患者样本进行了检测。我们发现，感染会增加胃内环境和全身循环中白细胞介素10（IL10）、IL6和TGF-β的产生。与IL6/IL10介导的JAK/STAT途径过度激活一起，感染会通过启动子区域的高甲基化导致细胞因子信号传导抑制因子1（SOCS1）基因失活。这项研究表明，在胃癌发生过程中，SOCS1介导的表观遗传沉默与炎性细胞因子共同导致JAK/STAT级联反应过度激活。
