RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model.
Cyclooxygenase
Diclofenac
Inflammation
Lipoxygenase
Phospholipase
RNA sequencing
Transcriptome
Traumeel
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
25 Nov 2021
25 Nov 2021
Historique:
received:
16
04
2021
accepted:
08
10
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
30
11
2021
Statut:
epublish
Résumé
Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products. Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12 and 192 h after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n = 7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach. At early time points (12-36 h), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue. Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad 'phytocellular' effect on the wound transcriptome by altering the balance of cell types present in the wound.
Sections du résumé
BACKGROUND
BACKGROUND
Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products.
METHODS
METHODS
Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12 and 192 h after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n = 7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach.
RESULTS
RESULTS
At early time points (12-36 h), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue.
CONCLUSIONS
CONCLUSIONS
Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad 'phytocellular' effect on the wound transcriptome by altering the balance of cell types present in the wound.
Identifiants
pubmed: 34823472
doi: 10.1186/s12864-021-08083-2
pii: 10.1186/s12864-021-08083-2
pmc: PMC8614049
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Biomarkers
0
Diclofenac
144O8QL0L1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
854Informations de copyright
© 2021. The Author(s).
Références
Clin Dev Immunol. 2004 Jun;11(2):143-9
pubmed: 15330450
Mol Aspects Med. 2017 Dec;58:1-11
pubmed: 28263773
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D258-61
pubmed: 14681407
Biochem Pharmacol. 2009 Feb 1;77(3):397-411
pubmed: 18996094
Free Radic Biol Med. 2017 Jan;102:87-99
pubmed: 27867096
Curr Pharm Des. 2018;24(14):1533-1550
pubmed: 29701147
Curr Drug Targets. 2014 Apr;15(4):410-22
pubmed: 24313690
Int Immunopharmacol. 2015 Sep;28(1):328-36
pubmed: 26122134
Mediators Inflamm. 2016;2016:1693918
pubmed: 27478305
Ann N Y Acad Sci. 2018 Nov;1431(1):3-13
pubmed: 30058075
J Biol Chem. 2016 Jul 22;291(30):15602-13
pubmed: 27226633
Nutr Metab (Lond). 2020 Jan 13;17:5
pubmed: 31956331
Curr Med Res Opin. 2010 Jul;26(7):1715-31
pubmed: 20470236
J Biol Chem. 2000 Apr 28;275(17):13000-6
pubmed: 10777602
Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):327-32
pubmed: 20227865
DNA Cell Biol. 2003 Aug;22(8):479-87
pubmed: 14565864
Biotechniques. 1995 Dec;19(6):942-5
pubmed: 8747660
J Immunol. 2014 Feb 15;192(4):1547-57
pubmed: 24403530
J Am Assoc Lab Anim Sci. 2007 Jan;46(1):58-65
pubmed: 17203918
Biotechnol Adv. 2018 Nov 1;36(6):1709-1723
pubmed: 29454981
Nat Prod Commun. 2013 Jan;8(1):105-8
pubmed: 23472470
Genome Biol. 2014;15(12):550
pubmed: 25516281
Exp Mol Pathol. 2017 Apr;102(2):337-346
pubmed: 28268192
N Engl J Med. 1986 Dec 25;315(26):1650-9
pubmed: 3537791
Sci Rep. 2018 Apr 3;8(1):5458
pubmed: 29615682
Adv Exp Med Biol. 1999;469:449-54
pubmed: 10667367
Drug Discov Today. 2014 Dec;19(12):1871-82
pubmed: 25172801
Nat Biotechnol. 2009 Jul;27(7):652-8
pubmed: 19581875
Front Genet. 2019 Jan 22;9:636
pubmed: 30723492
Front Immunol. 2020 Dec 04;11:603187
pubmed: 33343575
J Allergy Clin Immunol. 2021 Jan;147(1):199-212
pubmed: 32709423
Biochem J. 2012 Apr 15;443(2):451-61
pubmed: 22268508
Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551
pubmed: 33125081
Free Radic Biol Med. 2006 Apr 15;40(8):1281-92
pubmed: 16631518
Eur J Appl Physiol. 2017 Mar;117(3):591-605
pubmed: 28224232
J Dairy Sci. 2013 Feb;96(2):1038-43
pubmed: 23245956
Cell Immunol. 2011;271(2):379-84
pubmed: 21885043
NPJ Regen Med. 2018 Nov 7;3:21
pubmed: 30416753
Biochem Biophys Res Commun. 2016 Jan 15;469(3):521-8
pubmed: 26655811
Nutrients. 2021 Jan 12;13(1):
pubmed: 33445474
Free Radic Biol Med. 2015 Dec;89:1192-202
pubmed: 26546695
J Nat Prod. 2018 Mar 23;81(3):506-514
pubmed: 29215273
Chem Biol Interact. 2012 Aug 30;199(2):87-95
pubmed: 22735309
Eur J Med Chem. 2018 Jun 10;153:2-28
pubmed: 29329790
J Immunol. 2006 Jun 1;176(11):7051-61
pubmed: 16709867
Toxicol Lett. 2006 Sep 30;166(1):77-87
pubmed: 16859844
Free Radic Res. 1995 Mar;22(3):193-207
pubmed: 7757196
Mol Cell Biochem. 2016 Mar;414(1-2):23-36
pubmed: 26838169
BMC Biol. 2010 Dec 21;8:149
pubmed: 21176148
Crit Rev Biochem Mol Biol. 1995;30(6):445-600
pubmed: 8770536
BMC Genomics. 2017 Nov 7;18(1):850
pubmed: 29115927
Lasers Med Sci. 2014 Jan;29(1):257-65
pubmed: 23619627
Int J Mol Sci. 2020 Nov 20;21(22):
pubmed: 33233704
Front Mol Biosci. 2017 Aug 17;4:57
pubmed: 28879183
Int J Clin Pract. 2013 Oct;67(10):979-89
pubmed: 23889885