16th Annual Child Health Research Days

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Save the date: Oct. 6 & 7, 2021

Abstracts

#30 Chromofungin Regulates the Development of Experimental Colitis and Dendritic Cells


Kunal Kapoor, University of Manitoba; Nour Eissa, University of Manitoba; Mohammad Rabbi, University of Manitoba; Laetitia Kermarrec, University of Manitoba; Gaurav Gupta, University of Manitoba; Jude Uzonna, University of Manitoba; Jean Eric Ghia, University of Manitoba


Introduction

Inflammatory Bowel Disease (IBD) is characterized by altered levels of chromogranin-A (CHGA) and a dysregulation in the function of dendritic cells (DCs). CHGA be cleaved to several bioactive peptides including chromofungin (CHR) that is involved in immune regulation. We investigated the potential effects of CHR on the functional capacity of DCs during colitis.


Methods

Colitis was induced to C57BL/6 mice (7-8 weeks), 5% dextran sulfate sodium (DSS) for 5 days. Intra-rectal administration of CHR (2.5 mg/kg/day) was initiated one day before induction of colitis and severity of colitis was assessed using the disease activity index, the macroscopic and microscopic scores and colonic interleukin (IL)-6, IL-23, IL-12p40 and tumor necrosis factor (TNF)-alpha, using qRT-PCR/ELISA. Splenic CD11c+ cells isolated from naïve and colitic mice, were cultured with CHR (10-6 M) overnight and CD40, 80, 86 and MHC II markers were quantified using flow cytometry. Bone marrow DCs (BMDCs) were isolated from naïve mice and treated with CHR (10-6 M) overnight and then challenged overnight with 0.1% DSS and DCs surface markers, IL-12, 6 and TNF-alpha were quantified.


Results

CHR treatment reduced the severity of colitis. Disease activity index, macroscopic. microscopic scores, IL-6, IL-23, IL-12p40 and TNF-alpha were significantly decreased. Splenic CD11c+ cells isolated from colitic mice and treated in vitro with CHR demonstrated a significant reduction in the CD40 and CD80 surface markers when compared with control colitic group. MHCII and CD86 were not modified. In-vitro, in control conditions stimulation of naïve BMDCs with DSS demonstrated a significant increase of IL-12p40 without modifying IL-6, TNF-a and CD40, 80, 86, MHCII surface markers. Treatment with CHR didn’t modify any markers studied.


Conclusion

CHR regulates the intestinal inflammation and regulates the expression of specific CD markers. CHR demonstrates a protective by potentially targeting the DCs population, but further experiments are warranted.