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P065 Olfactory receptor, OR51E2 is a marker for innate immune cells in ulcerative colitis

B. J. Lee*1, N. J. Kim1, S. B. Park1, J. S. Koo1, Y. T. Jeen1, J. J. Park1, M. K. Joo1

1Korea University, Seoul, South Korea

Background

Olfactory receptors (ORs) are one of the largest gene family of human genome and the GPCRS. Ectopic expression of ORs have been detected in various tissue including testis, prostate, kidney and GI tracts. Previously, we identified meaningful expression of OR51E2 genes in UC patients using NGS sequencing. We aimed to determine the exact function and roles of OR51E2 in the pathogenesis of ulcerative colitis.

Methods

Immunohistochemical staining of OR51E2, CD 68, CD 163, CD 38, F 4/80 and syndecan-1 were evaluated in both human colon from ulcerative colitis and control and inflamed mice induced by 3% DSS colitis. Human monocyte cell line, THP-1 cells were differentiated to macrophage and polarised to M1 or M2 phenotypes using PMA. Expression of OR51E2 and macrophage marker were analysed by qPCR. To identify ligand for olfactory receptors, SCFAs (butylate, b-ionone, propionate) were treated in both NCM 460 cells and macrophages polarised from THP-1 cells with various concentration. OR51E2 were analysed by q PCR and immunocytochemistry. For in vivo study, SCFAs were administrated in WT mice and WT mice treated with 5 days of 3% DSS. Q PCR and IHC was done for OR51E2 and macrophage markers including F4/80 and CD 163.

Results

We found that UC patient had more OR51E2 protein expression in lamina propria compared with control group to control patients of normal colonic mucosa and the damaged mice mucosa induced by DSS. Immunohistochemical analysis revealed an increase in the proportion of CD 163 positive cells expressing of OR51E2 with about 70% of all OR51E2 positive lamina propria mono nuclear cells (p < 0.05). In case of mice colon, OR51E2 and CD 163 immunoreactivity were more colocalised in lamina propria compared with F4/80. The genetic expression of OR51E2 from M1 macrophage polarised from THP-1 cells was significantly down-regulated compared with the expression of M0 and M2 macrophage. Butylate treatment to M0 macrophages was significantly increase in M2 polarisation with an significant increase in OR51E expression but there was no butylate effect on the NCM 460 cells.

Conclusion

Taken together, our data suggest that ectopic OR51E2 can be a marker of innate immune cells and also be associated with M2 polarisation. SCFA as a ligand for OR51E2 can modulate colonic inflammation by affecting macrophage polarisation.