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Biomolecules 2018, 8(3), 59; https://doi.org/10.3390/biom8030059

The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis and Appendectomy

1
Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, NSW 2052, Australia
2
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
3
Department of Surgery, St. George Hospital, Kogarah, NSW 2217, Australia
*
Author to whom correspondence should be addressed.
Received: 13 June 2018 / Revised: 3 July 2018 / Accepted: 16 July 2018 / Published: 20 July 2018
(This article belongs to the Special Issue The Role of Chemokines in Inflammatory Pathologies)
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Abstract

The appendix contains abundant lymphoid tissue and is constantly exposed to gut flora. When completed at a young age, appendicitis followed by appendectomy (AA) prevents or significantly ameliorates Inflammatory Bowel Diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn’s disease and ulcerative colitis. Our murine AA model is the only existing experimental model of AA. In our unique model, AA performed in the most proximal colon limits colitis pathology in the most distal colon by curbing T-helper 17 cell activity, diminishing autophagy, modulating interferon activity-associated molecules, and suppressing endothelin vaso-activity-mediated immunopathology. In the research presented in this paper, we have examined the role of chemokines in colitis pathology with our murine AA model. Chemokines are a family of small cytokines with four conserved cysteine residues. Chemokines induce chemotaxis in adjacent cells with corresponding receptors. All 40 known chemokine genes and 24 chemokine receptor genes were examined for gene expression levels in distal colons three days post-AA and 28 days post-AA. At 28 days post-AA, the chemokine gene CCL5 was significantly upregulated. Furthermore, Gene Set Enrichment Analysis (GSEA) showed upregulation of seven CCL5-associated gene-sets 28 days post-AA in contrast to just one gene-set downregulated at the same time-point. The chemokine gene CXCL11 was significantly upregulated three days post-AA and 28 days post-AA. Evaluation using GSEA showed upregulation of six CXCL11-associated gene sets but no downregulation of any gene set. At 28 days post-AA, CCL17 gene expression was significantly downregulated. There was no expression of any chemokine receptor gene three days post-AA, but CCR10 was the only chemokine receptor gene that displayed differential gene expression (upregulation) 28 days post-AA. No CCR10-associated gene set was upregulated in GSEA in contrast to one downregulated gene set. Our analysis resulted in identifying three new therapeutic targets towards ameliorating colitis: CCL5, CXCL11, and CCL17. While CCL5 and CXCL11 are good therapeutic chemokine candidates to be exogenously administered, CCL17 is a good candidate chemokine to competitively inhibit or limit colitis pathology. View Full-Text
Keywords: appendectomy; appendicitis; chemokine; chemokine receptor; CCL5; CCL7; CCL8; CCL17; CCL20; CCR10; CXCL11; inflammatory bowel disease; ulcerative colitis appendectomy; appendicitis; chemokine; chemokine receptor; CCL5; CCL7; CCL8; CCL17; CCL20; CCR10; CXCL11; inflammatory bowel disease; ulcerative colitis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Cheluvappa, R.; Thomas, D.G.; Selvendran, S. The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis and Appendectomy. Biomolecules 2018, 8, 59.

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