Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof, Dr. Moestopo, No. 6-8, Surabaya, Surabaya 60131, Indonesia; Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia.
Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita 879-5593, Japan.
Cytokine. 2023 Mar;163:156122. doi: 10.1016/j.cyto.2022.156122. Epub 2023 Jan 12.
Helicobacter pylori infection is a major cause of intestinal metaplasia. In this study, we aimed to understand the reason underlying the low grade and incidence of intestinal metaplasia in Indonesia, based on the expression of genes encoding proinflammatory cytokines in gastric biopsy specimens. The possible reasons for the lesser virulence of the East-Asian-type CagA in Indonesia than that of the Western-type CagA, which is not common in other countries, were also investigated. The mRNA expression of cytokines was evaluated using real-time PCR. CagA characteristics were analyzed using in silico analysis. The expression of cytokines was typically not robust, among H. pylori-infected subjects in Indonesia, despite them predominantly demonstrating the East-Asian-type CagA. This might partially be explained by the characteristics of the East-Asian-type CagA in Indonesia, which showed a higher instability index and required higher energy to interact with proteins related to the cytokine induction pathway compared with the other types (p < 0.001 and p < 0.05, respectively). Taken together, besides the low prevalence of H. pylori, the low inflammatory response of the host and low CagA virulence, even among populations with high infection rates, may play an essential role in the low grade and low incidence of intestinal metaplasia in Indonesia. We believe that these findings would be relevant for better understanding of intestinal metaplasia, which is closely associated with the development of gastric cancer.
幽门螺杆菌感染是肠上皮化生的主要原因。在本研究中，我们旨在基于胃活检标本中编码促炎细胞因子的基因表达，了解印度尼西亚肠上皮化生发生率低和程度低的原因。还研究了印度尼西亚东亚型 CagA 比在其他国家不常见的西方型 CagA 的毒力较低的可能原因。使用实时 PCR 评估细胞因子的 mRNA 表达。使用计算机分析分析 CagA 特征。尽管印度尼西亚的大多数受试者表现出东亚型 CagA，但 CagA 感染患者的细胞因子表达通常不明显。这可能部分解释了印度尼西亚东亚型 CagA 的特点，与其他类型相比，东亚型 CagA 的不稳定性指数更高，与细胞因子诱导途径相关的蛋白质相互作用需要更高的能量（分别为 p < 0.001 和 p < 0.05）。总之，除了 H. pylori 的低流行率外，宿主的低炎症反应和低 CagA 毒力，即使在感染率高的人群中，也可能在印度尼西亚肠上皮化生程度低和发生率低中发挥重要作用。我们相信，这些发现对于更好地理解与胃癌发展密切相关的肠上皮化生将具有重要意义。
