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. 2020 Sep;20(3):1452-1462.
doi: 10.4314/ahs.v20i3.51.

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis

Fatemeh Azadegan-Dehkordi  1 , Ardeshir Abbasi  2 , Amin Talebi Bezmin Abadi  3 , Khaled Minooie  4 , Parya Aslani  5 , Razieh Sadat Hosseini  1 , Farid Zandi  3
Affiliations

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis

Fatemeh Azadegan-Dehkordi et al. Afr Health Sci. 2020 Sep.

Abstract

Background and objective: Chronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients.

Materials and methods: Total RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies.

Results: Results point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don't find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05).

Conclusion: These findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.

Keywords: Cytokines; IL-23, IL-17; gastritis; polymorphism.

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Figures

Fig. 1
Fig. 1
Schematic figure showing possible mechanism of polymorphism in IL-17A, IL-17F and IL-23 receptor that may affect some of the IL-17/IL-23 axis. IL-17/IL-23 axis is the key inflammatory pathway including main cytokines as TGF-β, IL-6, IL-17, IL-21 and IL-23. Polymorphisms in IL-17A, IL-17F and IL-23R were shown as pivotal site of IL-17/IL-23 that may affect expression of TGF-β, IL-6, IL-17, IL-21 and IL-23 separately.
Fig. 2
Fig. 2
PCR-RFLP polyacrylamide gel electrophoresis of the IL-17A G197A and IL-17F A7488G and IL23R +2199A/C (rs10889677) polymorphism indicating: (A) IL-17A G197A, No. 1, 2, 5, 9 (AA = 102 bp) 4, 7, 8 (AC = 102, 68, 34 bp) 3, 6 (GG = 68, 34 bp) genotypes and (B) IL-17F A7488G, No. 2, 4, 6 (AA = 80, 63 bp) 3, 7 (GA = 143, 80, 63 bp) 1, 5 (GG = 143 bp) genotypes and (C) IL23R +21199A/C (re10889677), No 1 (CC = 154, 61 bp), 2, 3, 4, 5 (AC = 215, 154, 61 bp), 6, 7 (AA = 215 bp) genotypes
Figure 3
Figure 3
Expression of cytokines in biopsies gastritis patients with SNPs in IL-17A G197Agene. Reverse transcription and quantitative PCR were performed to estimate the relative expression levels of each cytokine. Expression of TGF-β IL-6 (B), IL-17 (C), IL-21 (D) and IL-23 (E)were normalized with expression values of human β-actin. Difference in mRNA expression between patients with SNPs in IL-17A G197Awere not significant in gastritis patients. 0.05 > p was considered statistically significant using the Mann-Whitney test.
Figure 4
Figure 4
Expression of cytokines in biopsies gastritis patients with SNPs in IL-17F A7488G gene. Reverse transcription and quantitative PCR were performed to estimate the relative expression levels of each cytokine. Expression of TGF-β1 (A), IL-6 (B), IL-17 (C), IL-21 (D) and IL-23 (E)were normalized with expression values of human β-actin. Difference in mRNA expression between patients with SNPs in IL-17F A7488G were not significant in gastritis patients. 0.05 > p was considered statistically significant using the Mann-Whitney test.
Figure 5
Figure 5
Expression of cytokines in biopsies gastritis patients with SNPs in IL23R +2199A/C gene. Reverse transcription and quantitative PCR were performed to estimate the relative expression levels of each cytokine. Expression of TGF-β1 (A), IL-6 (B), IL-17 (C), IL-21 (D) and IL-23 (E)were normalized with expression values of human β-actin. Difference in mRNA expression between patients with SNPs in IL23R +2199A/A was significant in IL23 expression but don't observed significant between patients with other SNPs in gastritis patients. 0.05 > p was considered statistically significant using the Mann-Whitney test.
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