TY - JOUR
T1 - Low-grade intestinal metaplasia in Indonesia
T2 - Insights into the expression of proinflammatory cytokines during Helicobacter pylori infection and unique East-Asian CagA characteristics
AU - Miftahussurur, Muhammad
AU - Alfaray, Ricky Indra
AU - Fauzia, Kartika Afrida
AU - Dewayani, Astri
AU - Doohan, Dalla
AU - Waskito, Langgeng Agung
AU - Rezkitha, Yudith Annisa Ayu
AU - Utomo, Didik Huswo
AU - Somayana, Gde
AU - Fahrial Syam, Ari
AU - Lubis, Masrul
AU - Akada, Junko
AU - Matsumoto, Takashi
AU - Yamaoka, Yoshio
N1 - Funding Information:
The authors would like to thank Anggia Noor Ramadhani and Institut Bioinformatika Indonesia (INBIO-Indonesia) for their excellent teaching of the protein in silico analysis to Ricky Indra Alfaray. The authors would like to thank Hiroyuki Nagashima for his finest teaching of real time PCR to Ricky Indra Alfaray. The authors would also like to thank Saruuljavkhlan Batsaikhan for his support assistance. The authors also appreciate the support given by Thailand Science Research and Innovation Fundamental Fund, Bualuang ASEAN Chair Professorship at Thammasat University, and Center of Excellence in Digestive Diseases, Thammasat University, Thailand. Last but not least, the authors thank to all the funders that had been suporting this study. The funding of this study is mainly supported as mentioned in the Funding section.
Funding Information:
The authors would like to thank Anggia Noor Ramadhani and Institut Bioinformatika Indonesia (INBIO-Indonesia) for their excellent teaching of the protein in silico analysis to Ricky Indra Alfaray. The authors would like to thank Hiroyuki Nagashima for his finest teaching of real time PCR to Ricky Indra Alfaray. The authors would also like to thank Saruuljavkhlan Batsaikhan for his support assistance. The authors also appreciate the support given by Thailand Science Research and Innovation Fundamental Fund, Bualuang ASEAN Chair Professorship at Thammasat University, and Center of Excellence in Digestive Diseases, Thammasat University, Thailand. Last but not least, the authors thank to all the funders that had been suporting this study. The funding of this study is mainly supported as mentioned in the Funding section.
Funding Information:
This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (18KK0266, 19H03473, 21H00346 and 22H02871) (Yoshio Yamaoka), 17 K09353 (Junko Akada), and 18 K16182 (Takashi Matsumoto). Ricky Indra Alfaray is Ph.D. candidate supported by MEXT Scholarship since October 2019. In addition, this study also supported by Indonesian Research Collaboration No. 1073/UN3.15/PT/2022 (Muhammad Miftahussurur, Ari Fahrial Syam, Masrul Lubis). This work was also supported by Japan Agency for Medical Research and Development (AMED) [e-ASIA JRP] (22jm0210090h0002) (Yoshio Yamaoka).
Publisher Copyright:
© 2022
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - CagA
KW - Helicobacter pylori
KW - Indonesia
KW - Intestinal metaplasia
KW - Proinflammatory cytokines
UR - http://www.scopus.com/inward/record.url?scp=85146184019&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2022.156122
DO - 10.1016/j.cyto.2022.156122
M3 - Article
AN - SCOPUS:85146184019
SN - 1043-4666
VL - 163
JO - Cytokine
JF - Cytokine
M1 - 156122
ER -
