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P846 Elafin-expressed Escherichia coli Nissle 1917 ameliorates experimental colitis in mice

G. Teng*1, L. Yun1, W. Ting1, W. Huahong1

1Peking University First Hospital, Gastroenterology, Beijing, China

Background

The decrease of Elafin is associated with several inflammatory diseases. Elafin up-regulated EGFR-PI3K-Akt pathway, inhibiting pulmonary inflammation. Escherichia coli Nissle 1917 (EcN) is a probiotic not inferior to the established standard 5-ASA for maintenance of remission in UC. In this study, we confirm the anti-inflammation mechanism of Elafin in colon cells and evaluate the anti-colitis effects of Elafin-expressed EcN in dextran sulphate sodium (DSS)-induced colitis mouse model.

Methods

In vitro, we used lentivirus-mediated gene transfer system to transfer Elafin gene into Caco2 cells. And the mRNA levels of EGFR, PI3K and Akt was determined by qRT-PCR. Meanwhile we used genetical technology to obtain the genetical EcN expressed Elafin. C57BL/6 mice were administered intra-gastrically with either EcN-Elafin (1 × 109 CFU/ml), EcN (1 × 109 CFU/ml) or mesalazine (822 mg/kg) for 10 days. Acute colitis was induced by 3% dextran sulphate sodium (DSS) drinking water for 7 days. After mice were sacrificed, HE staining was performed in colon tissues to estimate mucosal injury.

Results

The Elafin-expressed cells and probiotic were constructed successfully (Figure 1A and B)

Figure 1. Elafin activates EGFR-PI3K-Akt pathway. The Elafin-expressed cells (A) and probiotic (B) were constructed. EGFR, PI3K and Akt mRNA levels of Elafin-expressed cells was determined by qRT-PCR(C). *p < 0.05. ns, not significant.

In Caco2 cells, up-regulated Elafin can lead to high mRNA levels of EGFR, PI3K and Akt (Figure 1C). In mouse model, colon length of EcN-Elafin group and EcN group was longer than DSS group, which was similar to mesalazine group (Figure 2A). EcN-Elafin group and EcN group reduced DSS-induced colon injury, which was similar to mesalazine group (Figure 2B)

Figure 2. EcN-Elafin reduced DSS-induced colon damage. (A)The pictures and column chart of colon length in each group was displayed. (B) Typical microscopic images by HE staining of colon tissues. Scale bar: 200 μm. *p < 0.05. ns, not significant.

Conclusion

The genetical EcN expressed Elafin reduced DSS-induced colon damage. Elafin also up-regulate EGFR-PI3K-Akt pathway in colon cells.