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P771 The recombinant NZ9000SHD-5 attenuates the inflammation and mucosal lesions in dextran sodium sulfate-induced colitis

Zeng L., Chen Y.

Nanfang Hospital, Department of Gastroenterology, Guangzhou, China

Background

Defensin, as a family member of antimicrobial peptide, plays an important role in host immunity and maintaining the gut barrier function. Meanwhile, probiotics were reported to be a protective role in patients of IBD.

Methods

In this study, we optimized a defensin mHD-5 mainly consisted by the mature peptide of human defensin 5 (HD-5) and constructed vector-pN8148-SHD-5 and transfected into Lactococcus lactis to build the recombinant NZ9000SHD-5 based on the nisin-controlled gene expression and gene splicing technology.

Results

We found that recombinant NZ9000SHD-5 attenuated imflammatory cells infiltration, histopathological changes in colonic gland, and protected the intensity of epitheal cells in DSS-induced colitis. Recombinant NZ9000SHD-5 remarkably suppressed the production of inflammatory cytokine, such as interleukin-1B (IL-1B), IL-6 and tumor necrosis factor-alpha (TNF-α). Meamwhile, NZ9000SHD-5 increased the expression of zonula occcludens-1 and occluding mRNA and proteins, and it decreased the permeability of FITC-D while preserving the structure and function of Tight junctions in the DSS-induced models. We tested the mechanism of protective effects of NZ9000SHD-5 on LPS-induced model of mouse macrophage RAW264.7 cell. Pretreated with the supernatant of NZ9000SHD-5 for 4h before exposed to LPS significantly reduce the concentrations of IL-6, IL-1B and TNF-α, inhibited the expression of LPS-induced phosphorylation nuclear transcription factor-kappa B (NF-κB) p65 protein and its inhibitor IκBα of NF-κB signaling pathways. In accordance with the protective effect of NZ9000SHD-5 on gut barrier of DSS-induced colitis, we observed the positive effect of NZ9000SHD-5 in mucosal injury and the disruption of epithelial barrier on Caco-2 cells. We found that NZ9000SHD-5 increased the transepithelial electrical resistance, and it decreased the permeability of FITC-D and the damage the of skeleton of TJs against the dextran sodium sulfate

Conclusion

The results indicate that the NZ9000SHD-5 relieves the changes in DSS-induced mucosal damage and paracellular permeability possibly through attenuating the colon inflammation by downregulating the activation of NF-KB signaling pathway, and therefore the administration of NZ9000SHD-5 may be a possible option for colitis.