PMID- 30037025
OWN - NLM
STAT- MEDLINE
DCOM- 20190918
LR  - 20190918
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 8
IP  - 3
DP  - 2018 Jul 20
TI  - The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis 
      and Appendectomy.
LID - 10.3390/biom8030059 [doi]
LID - 59
AB  - 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.
FAU - Cheluvappa, Rajkumar
AU  - Cheluvappa R
AUID- ORCID: 0000-0002-3472-9591
AD  - Department of Medicine, St. George Clinical School, University of New South 
      Wales, Sydney, NSW 2052, Australia. rajkumarchel@gmail.com.
FAU - Thomas, Dennis G
AU  - Thomas DG
AD  - Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 
      99352, USA. dennis.thomas@pnnl.gov.
FAU - Selvendran, Selwyn
AU  - Selvendran S
AUID- ORCID: 0000-0001-9888-3574
AD  - Department of Surgery, St. George Hospital, Kogarah, NSW 2217, Australia. 
      tselvendran@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180720
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Chemokines)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Appendectomy
MH  - Appendicitis/genetics/immunology/*surgery
MH  - Chemokines/*genetics/metabolism
MH  - Colitis, Ulcerative/genetics/*immunology
MH  - Disease Models, Animal
MH  - Gene Expression Profiling/*methods
MH  - Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Mice
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, Chemokine/*genetics/metabolism
MH  - Th17 Cells/immunology
PMC - PMC6165111
OTO - NOTNLM
OT  - CCL17
OT  - CCL20
OT  - CCL5
OT  - CCL7
OT  - CCL8
OT  - CCR10
OT  - CXCL11
OT  - appendectomy
OT  - appendicitis
OT  - chemokine
OT  - chemokine receptor
OT  - inflammatory bowel disease
OT  - ulcerative colitis
COIS- We acknowledge Michael Grimm for overseeing us. Over the past couple of years, he 
      has not responded to emails, phone calls, and text messages to discuss 
      participation in manuscript writing, support, or co-authorship.
EDAT- 2018/07/25 06:00
MHDA- 2019/09/19 06:00
PMCR- 2018/09/01
CRDT- 2018/07/25 06:00
PHST- 2018/06/13 00:00 [received]
PHST- 2018/07/03 00:00 [revised]
PHST- 2018/07/16 00:00 [accepted]
PHST- 2018/07/25 06:00 [entrez]
PHST- 2018/07/25 06:00 [pubmed]
PHST- 2019/09/19 06:00 [medline]
PHST- 2018/09/01 00:00 [pmc-release]
AID - biom8030059 [pii]
AID - biomolecules-08-00059 [pii]
AID - 10.3390/biom8030059 [doi]
PST - epublish
SO  - Biomolecules. 2018 Jul 20;8(3):59. doi: 10.3390/biom8030059.