Gut Liver. 2020;14(6):735-745.

Helicobacter pylori Eradication Induced Constant Decrease in Interleukin- 1B Expression over More Than 5 Years in Patients with Gastric Cancer and Dysplasia.

, , , , ,

제1저자 김희진 · 교신저자 김나영, 이옥재

PMID 32703913 PMC7667922 DOI 10.5009/gnl19312 IF 4.1 소화기내과

소속 (5)

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju, Korea.

Abstract

BACKGROUND/AIMS Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H⁺, K⁺-adenosine triphosphatase (H⁺, K⁺-ATPase) and stimulating interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H⁺, K⁺-ATPase and IL-1β after Hp eradication.

METHODS Two hundred twentyone subjects were categorized as Hp-negative (n=84) or Hppositive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H⁺, K⁺-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction.

RESULTS The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hperadicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3-4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant.

CONCLUSIONS Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication.

Keywords

Gastric acidH(+)-K(+)-exchanging ATPaseHelicobacter pyloriInterleukin-1 beta

Figures

**Fig. 1** Proposed study algorithm for the inclusion and classification of subjects. Hp, *Helicobacter pylori*; IM, intestinal metaplasia; GC, gastric cancer.

**Fig. 2** Comparisons of the mRNA levels of *IL-1B* and *ATP4A* at baseline between the *Helicobacter pylori* (Hp)-negative and -positive groups. (A) Significantly higher levels of *IL-1B* mRNA were detected in the Hp-positive group than in the Hp-negative group (p<0.001). (B) The differences between Hp-negative and -positive groups were significant within the intestinal metaplasia (IM)-negative (p=0.016), (C) non-gastric cancer (GC)/dysplasia (p=0.009) and GC/dysplasia subgroups (p=0.033). (D-F) No significant differences in baseline ATP4A mRNA levels were observed between the Hp-positive and Hp-negative groups. Data are presented as the means±standard errors.

**Fig. 3** Changes in the mRNA levels of *IL-1B* and *ATP4A* over time in the *Helicobacter pylori* (Hp)-negative and -eradicated groups. (A) The *IL-1B* mRNA levels at all time points after Hp eradication were not significantly lower than the values at baseline. The difference in *IL-1B* mRNA level between the Hp-negative and -eradicated groups disappeared 1 year after eradication. The level of *IL-1B* mRNA at 3–4 years after eradication was significantly higher than the baseline value in the Hp-negative group (p=0.016). (B) No significant changes over time in the *ATP4A* mRNA level were detected compared to the baseline value in Hp-eradicated group, except at 3–4 years after eradication (p=0.049). Significant differences in the *ATP4A* mRNA level were not observed between the Hp-negative and -positive groups at any time point. Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects; ^†p-value <0.05 compared to baseline level in Hp-eradicated subjects.

**Fig. 4** Changes in the mRNA levels of *IL-1B* over time within the intestinal metaplasia (IM)-negative and -positive subgroups. No significant changes in the mRNA levels of *IL-1B* after *Helicobacter pylori* (Hp) eradication were measured compared with the values measured before Hp eradication at all follow-up time points within the IM-negative (A) and IM-positive (B) subgroups. Within the IM-negative subgroup, the difference in *IL-1B* mRNA levels between the Hp-negative and -eradicated groups disappeared 1 year after eradication. The mRNA level of *IL-1B* 3-4 years after Hp eradication was significantly higher than the baseline value in the IM-negative and Hp-negative groups (p=0.011). Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects.

**Fig. 5** Changes in the mRNA levels of *IL-1B* over time within the non-gastric cancer (GC)/dysplasia and GC/dysplasia subgroups. (A) Within the non-GC/dysplasia subgroup, the *IL-1B* mRNA level 3–4 years after *Helicobacter pylori* (Hp) eradication was significantly higher than the level before Hp eradication (p=0.049). Compared to the baseline level, significantly higher mRNA levels of *IL-1B* were found 1 year (p=0.001), 3–4 years (p=0.001) and ≥5 years (p=0.011) after eradication in the GC/dysplasia-negative and Hp-negative subgroups. (B) *IL-1B* mRNA was expressed at significantly lower levels at all follow-up time points after Hp eradication compared with the values measured before Hp eradication in the GC/dysplasia subgroup (p<0.05 for all intervals). The differences in *IL-1B* mRNA levels between the Hp-negative and -eradicated groups were not significant within the non-GC/dysplasia and GC/dysplasia subgroups at all time points. Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects; ^†p-value <0.05 compared to baseline level in Hp-eradicated subjects.

**Fig. 6** Changes in the mRNA levels of *ATP4A* over time within the intestinal metaplasia (IM)-negative and -positive subgroups. No significant changes in the mRNA levels of *ATP4A* after *Helicobacter pylori* (Hp) eradication were measured compared with the values measured before Hp eradication at all follow-up time points within the IM-negative (A) and IM-positive (B) subgroups. Within the IM-negative subgroup, the mRNA level of *ATP4A* 3–4 years after eradication was significantly higher than the baseline level in the Hp-negative group (p=0.033). Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects.

**Fig. 7** Changes in the mRNA levels of *ATP4A* over time within the non-gastric cancer (GC)/dysplasia and GC/dysplasia subgroups. The mRNA level of *ATP4A* 2 years after *Helicobacter pylori* (Hp) eradication was significantly lower than the baseline level within the GC/dysplasia subgroup (p=0.012); at all other time points, no significant changes in the *ATP4A* mRNA level were detected after Hp eradication in the subgroups stratified by the presence of GC/dysplasia. In the Hp-negative group, significant differences in the *ATP4A* mRNA level were found 3–4 years after eradication in the non-GC/dysplasia subgroup (p=0.027) and ≥5 years in the GC/dysplasia subgroup (p=0.007) compared to the baseline values. Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects; ^†p-value <0.05 compared to baseline level in Hp-eradicated subjects.

**Fig. 8** Changes in serum pepsinogen (PG) I (A) and II (B) levels and the PG I/II ratio (C) over time. Significantly lower PG II levels and higher PG I/II ratios were observed at all follow-up time points after *Helicobacter pylori* (Hp) eradication compared with the values measured before Hp eradication. Data are presented as the means±standard errors. *p-value <0.05 compared to baseline level in Hp-negative subjects; ^†p-value <0.05 compared to baseline level in Hp-eradicated subjects.

그림 출처: PubMed Central 공개 논문 (PMC7667922)

Conflict of interest statement

CONFLICTS OF INTEREST. No potential conflict of interest relevant to this article was reported.

그 밖의 정보