3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 06 2022
08 06 2022
Historique:
received:
21
12
2021
accepted:
13
05
2022
entrez:
8
6
2022
pubmed:
9
6
2022
medline:
11
6
2022
Statut:
epublish
Résumé
In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowel diseases where dysbiosis has been described. Our aim was to identify which signalling pathways are involved in this effect. We observed that 3-oxo-C12:2-HSL decreases expression of pro-inflammatory cytokines such as Interleukine-1β (- 35%) and Tumor Necrosis Factor-α (TNFα) (- 40%) by stimulated immune RAW264.7 cells and decreased TNF secretion by stimulated PBMC in a dose-dependent manner, between 25 to 100 µM. Transcriptomic analysis of RAW264.7 cells exposed to 3-oxo-C12:2-HSL, in a pro-inflammatory context, highlighted JAK-STAT, NF-κB and TFN signalling pathways and we confirmed that 3-oxo-C12:2-HSL inhibited JAK1 and STAT1 phosphorylation. We also showed through a screening assay that 3-oxo-C12:2-HSL interacted with several human bitter taste receptors. Its anti-inflammatory effect involved TAS2R38 as shown by pharmacologic inhibition and led to an increase in intracellular calcium levels. We thus unravelled the involvement of several cellular pathways in the anti-inflammatory effects exerted by the QS molecule 3-oxo-C12:2-HSL.
Identifiants
pubmed: 35676403
doi: 10.1038/s41598-022-13451-3
pii: 10.1038/s41598-022-13451-3
pmc: PMC9177545
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Homoserine
6KA95X0IVO
4-Butyrolactone
OL659KIY4X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9440Informations de copyright
© 2022. The Author(s).
Références
J Gen Physiol. 2017 Feb;149(2):181-197
pubmed: 28053191
Nat Rev Gastroenterol Hepatol. 2020 Apr;17(4):223-237
pubmed: 32076145
Infect Immun. 2005 Mar;73(3):1648-55
pubmed: 15731065
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6
pubmed: 18936492
Infect Immun. 1998 Jan;66(1):36-42
pubmed: 9423836
ACS Infect Dis. 2018 Jul 13;4(7):1146-1156
pubmed: 29799189
Bioinformatics. 2017 Feb 1;33(3):414-424
pubmed: 27694195
PLoS One. 2011;6(5):e20123
pubmed: 21629661
Int Immunopharmacol. 2019 Sep;74:105724
pubmed: 31272064
J Immunol. 2013 Jul 1;191(1):337-44
pubmed: 23720811
Gut. 2013 Apr;62(4):531-9
pubmed: 22993202
Infect Immun. 2004 Nov;72(11):6463-70
pubmed: 15501777
ACS Cent Sci. 2020 Feb 26;6(2):197-206
pubmed: 32123737
Ann Gastroenterol. 2021 Sep-Oct;34(5):612-624
pubmed: 34475731
Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G59-73
pubmed: 27229123
PLoS One. 2016 Feb 11;11(2):e0147468
pubmed: 26866366
Front Immunol. 2018 Dec 11;9:2949
pubmed: 30619309
PLoS One. 2017 Sep 13;12(9):e0181302
pubmed: 28902853
Science. 2008 Jul 11;321(5886):259-63
pubmed: 18566250
Microbiome. 2020 Feb 3;8(1):12
pubmed: 32014035
Oncogene. 2004 Jun 17;23(28):4894-902
pubmed: 15064716
Microbiome. 2020 Feb 21;8(1):23
pubmed: 32085816
Cell Rep. 2015 Mar 24;10(11):1861-71
pubmed: 25801025
Science. 2019 Dec 20;366(6472):
pubmed: 31857448
Genome Biol. 2014;15(12):550
pubmed: 25516281
Anal Bioanal Chem. 2008 Jul;391(5):1619-27
pubmed: 18408921
Front Immunol. 2015 Jul 24;6:369
pubmed: 26257736
Gastroenterology. 2021 Jan;160(2):524-537
pubmed: 33253681
Infect Immun. 1999 Jan;67(1):206-12
pubmed: 9864217
J Bacteriol. 2013 Jan;195(2):173-9
pubmed: 23144246
Nat Med. 2016 Jun;22(6):598-605
pubmed: 27158904
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Nature. 2019 May;569(7758):655-662
pubmed: 31142855
PLoS One. 2018 Aug 29;13(8):e0202587
pubmed: 30157234
Assay Drug Dev Technol. 2014 Aug;12(6):342-51
pubmed: 25105973
Biochem J. 2011 Aug 15;438(1):33-7
pubmed: 21592089
Molecules. 2016 Mar 03;21(3):306
pubmed: 26950109
J Neurosci. 2012 Oct 3;32(40):13819-40
pubmed: 23035093
Biochem Pharmacol. 2015 Sep 15;97(2):173-7
pubmed: 26206195
J Clin Invest. 2012 Nov;122(11):4145-59
pubmed: 23041624
Tissue Barriers. 2020 Oct 1;8(4):1832877
pubmed: 33100129
Curr Opin Gastroenterol. 2010 Jul;26(4):327-31
pubmed: 20445446
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
J Crohns Colitis. 2019 Feb 1;13(2):144-164
pubmed: 30137275
Bioinformatics. 2013 Nov 1;29(21):2810-1
pubmed: 23958726
Chem Senses. 2010 Feb;35(2):157-70
pubmed: 20022913
Science. 1994 Jun 3;264(5164):1415-21
pubmed: 8197455
Curr Opin Pharmacol. 2021 Jun;58:68
pubmed: 33932913
Gastroenterol Clin North Am. 2020 Dec;49(4):739-752
pubmed: 33121693
PLoS One. 2015 Mar 17;10(3):e0119471
pubmed: 25780927
Nat Rev Gastroenterol Hepatol. 2017 Jan;14(1):9-21
pubmed: 27848962
Chem Senses. 2011 Jul;36(6):527-37
pubmed: 21422378
Microbes Infect. 2010 Nov;12(12-13):1042-50
pubmed: 20659582
Can J Microbiol. 2002 Apr;48(4):374-8
pubmed: 12030712
Front Immunol. 2020 Aug 28;11:1827
pubmed: 32983093
Gut. 2016 Mar;65(3):415-425
pubmed: 26045134
J Innate Immun. 2019;11(3):263-279
pubmed: 30428481
J Clin Med. 2020 Apr 28;9(5):
pubmed: 32354192
Microbes Infect. 2010 Mar;12(3):231-7
pubmed: 20074659
Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165646
pubmed: 31870715
Exp Biol Med (Maywood). 2015 Jul;240(7):896-903
pubmed: 25749498
Oncotarget. 2016 Mar 15;7(11):12623-32
pubmed: 26862855
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Nat Rev Gastroenterol Hepatol. 2020 Jun;17(6):323-337
pubmed: 32203403
Inflamm Res. 2020 Dec;69(12):1163-1172
pubmed: 32886145
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
J Bacteriol. 2008 Jul;190(13):4408-15
pubmed: 18178738
Nucleic Acids Res. 2019 Jan 8;47(D1):D1179-D1185
pubmed: 30357384
Int J Mol Sci. 2020 Dec 11;21(24):
pubmed: 33322538
Front Immunol. 2019 May 24;10:1084
pubmed: 31178859