ReferenceID 6232
Presence of PTPN2 SNP rs1893217 Enhances the Anti-inflammatory Effect of Spermidine
Inflamm Bowel Dis
BACKGROUND: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding PTPN2 represents a risk factor for inflammatory bowel disease (IBD). Our previous work demonstrated reduced PTPN2 activity and
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- Reference Id
- 6232
- Evidence Id
- 22822
- Core Evidence Id
- 22822
- Source Reference Id
- 5742
- Herb2 Reference Id
- HBREF006539
- Subject Paper Key
- HBIN044493_32031616
- Pubmed Id
- 32031616
- Doi
- 10.1093/ibd/izaa013
- Paper Title
- Presence of PTPN2 SNP rs1893217 Enhances the Anti-inflammatory Effect of Spermidine
- Paper Abstract
- BACKGROUND: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding PTPN2 represents a risk factor for inflammatory bowel disease (IBD). Our previous work demonstrated reduced PTPN2 activity and subsequently increased inflammatory signaling upon presence of SNP rs1893217. The naturally occurring polyamine spermidine reduces pro-inflammatory signaling via induction of PTPN2 activity; however, the effect of SNP rs1893217 on the anti-inflammatory potential of spermidine is still unknown. Here, we investigated how presence of SNP rs1893217 affects treatment efficacy of spermidine and whether it might serve as a potential biomarker for spermidine treatment. METHODS: Human T84 (wild-type [WT] for PTPN2 SNP rs1893217) and HT29 (heterozygous for PTPN2 SNP rs1893217) intestinal epithelial cells (IECs) were treated with several polyamines from the putrescine-spermidine pathway. T84 and HT29 IECs, THP-1 monocytes (WT and transfected with a lentiviral vector expressing PTPN2 SNP rs1893217) and genotyped, patient-derived peripheral blood mononuclear cells were challenged with IFN-gamma and/or spermidine. RESULTS: Among the analyzed polyamines, spermidine was the most efficient activator of PTPN2 phosphatase activity, regardless of the PTPN2 genotype. Spermidine suppressed IFN-gamma-induced STAT1 and STAT3 phosphorylation, along with decreased mRNA expression of ICAM-1, NOD2, and IFNG in IECs and monocytes. Of note, these effects were clearly more pronounced when the disease-associated PTPN2 C-variant in SNP rs1893217 was present. CONCLUSIONS: Our data demonstrate that spermidine is the most potent polyamine in the putrescine-spermine axis for inducing PTPN2 enzymatic activity. The anti-inflammatory effect of spermidine is potentiated in the presence of SNP rs1893217, and this SNP might thus be a useful biomarker for possible spermidine-treatment in IBD patients.
- Journal
- Inflamm Bowel Dis
- Publish Year
- 2020
- Experiment Subject
- human; patient; ht29 iecs; human t84; thp-1 monocytes
- Experiment Type
- Cell Experiment
- Phenotype Related
- Inflammatory Bowel Disease
- Paper Title Cn
- Paper Title En
- Presence of PTPN2 SNP rs1893217 Enhances the Anti-inflammatory Effect of Spermidine
- Bilingual Status
- semi_complete