Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7, 434
eCollection

Gastric TFF1 Expression From Acute to Chronic Helicobacter Infection

Affiliations

Gastric TFF1 Expression From Acute to Chronic Helicobacter Infection

Roberta Esposito et al. Front Cell Infect Microbiol.

Abstract

TFF1, a mucin-associated secreted peptide of gastric mucous cells, is known as a protective agent for stomach epithelium under different stimuli, but its role upon Helicobacter infection is still not clear. In this paper we characterized TFFs expression, with particular attention to TFF1, under Helicobacter infection in gastric cell lines. A mouse model was used to distinguish TFF1 mRNA expression between acute and chronic stages of Helicobacter infection. Our results show that TFF1 expression is induced in infected cells; in addition, the inflammatory response upon Helicobacter infection is inversely associated to pre-existing TFF1 protein levels. In infected mice, TFF1 is initially upregulated in gastric antrum in the acute phase of infection, along with IL-1β and IL-6. Then, expression of TFF1 is gradually silenced when the infection becomes chronic and IFN-γ, CXCL5, and CXCL15 reach higher levels. Our data suggest that TFF1 might help cells to counteract bacteria colonization and the development of a chronic inflammation.

Keywords: Helicobacter infection; TFF1; acute infection; chronic infection; cytokines; trefoil factors.

Figures

Figure 1
Figure 1
TFF1 and IL-8 transcriptional regulation upon H. pylori infection in KATO III and AGS cells. Real Time PCR analysis of IL-8 (A–C) and TFF1 (B–D) in KATO III and AGS gastric cancer cells after 36 h of H. pylori infection. (E) Western blot analysis of intracellular and secreted TFF1 protein in AGS cell line. (F) Densitometric analysis of intracellular protein signals. Experiments were carried out at least in triplicate and data are expressed as mean ± SD (t-test, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001).
Figure 2
Figure 2
TFF2 and TFF3 transcriptional regulation upon H. pylori infection in KATO III and AGS cells. Real-time PCR analysis of TFF2 and TFF3 mRNA after 36 h of H. pylori infection in AGS (A,B) and KATO III cells (C,D). Experiments were carried out at least in triplicate and data are expressed as mean ± SD. (t-test, *p ≤ 0.05; ***p ≤ 0.001, ****p ≤ 0.0001).
Figure 3
Figure 3
Trefoil factors and cytokines transcriptional regulation upon H. pylori infection in AGS-AC1 clone. Real-time PCR analysis of IL-8 (A), IL-6 (B), TFF1 (C), TFF2 (D) and TFF3 (E) mRNA after 36 h of H. pylori infection in AGS-AC1 cells induced or not with Doxycycline to express TFF1. Experiments were carried out at least in triplicate and data are expressed as mean ± SD (t-test, *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001, ****p ≤ 0.0001).
Figure 4
Figure 4
Trefoil Factors transcriptional regulation upon Helicobacter felis infection in C57BL/6 mice. Real Time PCR analysis of TFF1 (A), TFF2 (B), and TFF3 (C) mRNA in gastric antrum of C57BL/6 mice infected with H. felis and sacrificed at the indicated times (d = days; w = weeks) post-infection compared to naïve mice (n: 6–10 for each group). Data are mean ± SEM. (t-test, *p ≤ 0.05, **p ≤ 0.01; ***p ≤ 0.001, ****p ≤ 0.0001).
Figure 5
Figure 5
Transcriptional regulation of different cytokines upon Helicobacter felis infection in C57BL/6 mice. Real Time PCR analysis of IL-1β (A), IL-6 (B), INF-γ (C), CXCL5 (D), and CXCL15 (E) mRNA in gastric antrum of C57BL/6 mice infected with H. felis and sacrificed at the indicated times post-infection compared to naïve mice (n: 6–10 for each group). Data are mean ± SEM. (t-test, *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001).
Figure 6
Figure 6
H&E and immunofluorescence analysis of C57BL/6 gastric corpus mucosae representative regions. (A,E,I) naïve mice; (B,F,J) 5 days; (C,G,K) 8 days; (D,H,L) 6 weeks H. felis-infected mice. Staining shows no significant pathological changes in naïve mice. Note the inflammatory cell infiltration in the submucosa (20x magnifications of boxed sections, black arrows) and the positive staining for GR-1 (green) and F4/80 (red) after 5 days and progressively more significant at 6 weeks post-infection. (A–D) 10x; (E–L) 40x. Hoechst for nuclei (blue). Scale bar: 50 μm.

Similar articles

See all similar articles

Cited by 1 PubMed Central articles

References

    1. Aihara E., Engevik K. A., Montrose M. H. (2017). Trefoil factor peptides and gastrointestinal function. Annu. Rev. Physiol. 79, 357–380. 10.1146/annurev-physiol-021115-105447 - DOI - PMC - PubMed
    1. Bulitta C. J., Fleming J. V., Raychowdhury R., Taupin D., Rosenberg I., Wang T. C. (2002). Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element. Biochem. Biophys. Res. Commun. 293, 366–374. 10.1016/S0006-291X(02)00199-7 - DOI - PubMed
    1. Calvet X., Ramírez Lázaro M. J., Lehours P., Mégraud F. (2013). Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 18(Suppl. 1), 5–11. 10.1111/hel.12071 - DOI - PubMed
    1. Carvalho R., Kayademir T., Soares P., Canedo P., Sousa S., Oliveira C., et al. (2002). Loss of heterozygosity and promoter methylation, but not mutation, may underlie loss of TFF1 in gastric carcinoma. Lab. Invest. 82, 1319–1326. 10.1097/01.LAB.0000029205.76632.A8 - DOI - PubMed
    1. Cover T. L., Blaser M. J. (2009). Helicobacter pylori in health and disease. Gastroenterology 136, 1863–1873. 10.1053/j.gastro.2009.01.073 - DOI - PMC - PubMed

Publication types

MeSH terms

Feedback