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Inverse Expression of Prostaglandin E2-Related Enzymes Highlights Differences Between Diverticulitis and Inflammatory Bowel Disease

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Abstract

Background

Prostaglandin E2 (PGE2) is the dominant prostaglandin in the colon and is associated with colonic inflammation. PGE2 levels are regulated not only by cyclooxygenases (COX-1 and COX-2) but also by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the major PGE2-degrading enzyme. Information about the involvement of 15-PGDH in colonic inflammation is sparse.

Aim

We thus aimed to determine the gene expression and immunoreactivity (IR) of COX-1, COX-2, and 15-PGDH in colonic mucosa from patients with diverse inflammatory disorders: ulcerative colitis (UC), Crohn’s disease (CD), and acute diverticular disease (DD).

Methods

RNA from human colonic mucosa was extracted and assessed for gene expression by real-time PCR. Intact colon sections were processed for immunohistochemistry with immunostaining of the mucosal areas quantified using ImageJ.

Results

In colonic mucosa of both UC and CD, COX-2 mRNA and COX-2-IR were significantly increased, whereas 15-PGDH mRNA and 15-PGDH-IR were significantly reduced. In macroscopically undamaged acute DD mucosa, the opposite findings were seen: for both gene expression and immunoreactivity, there was a significant downregulation of COX-2 and upregulation of 15-PGDH. COX-1 mRNA and COX-1-IR remained unchanged in all diseases.

Conclusions

Our study for the first time demonstrated differential expression of the PGE2-related enzymes COX-2 and 15-PGDH in colonic mucosa from UC, CD, and acute DD. The reduction of 15-PGDH in IBD provides an additional mechanism for PGE2 increase in IBD. With respect to DD, alterations of PGE2-related enzymes suggest that a low PGE2 level may precede the onset of inflammation, thus providing new insight into the pathogenesis of DD.

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Acknowledgments

This study was supported by the National Health and Medical Research Council of Australia (ID APP568861). We thank Fei Shang and the Histology and Microscopy Unit for technical assistance and Changfa Qu for specimen collection.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia

    Liying Dai, Elizabeth Burcher & Lu Liu

  2. Department of Surgery, St George Hospital, Sydney, NSW, 2217, Australia

    Denis W. King, D. Shevy Perera & David Z. Lubowski

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  1. Liying Dai
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  2. Denis W. King
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  3. D. Shevy Perera
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  4. David Z. Lubowski
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Correspondence to Lu Liu.

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Dai, L., King, D.W., Perera, D.S. et al. Inverse Expression of Prostaglandin E2-Related Enzymes Highlights Differences Between Diverticulitis and Inflammatory Bowel Disease. Dig Dis Sci 60, 1236–1246 (2015). https://doi.org/10.1007/s10620-014-3478-7

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  • DOI: https://doi.org/10.1007/s10620-014-3478-7

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