Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.
CCL20
Glucocorticoid receptor
Inflammatory stimuli
Medroxyprogesterone acetate
Norethisterone
Synergism
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
received:
20
07
2022
revised:
29
11
2022
accepted:
12
01
2023
pmc-release:
01
03
2024
pubmed:
17
1
2023
medline:
2
2
2023
entrez:
16
1
2023
Statut:
ppublish
Résumé
The pro-inflammatory cytokine, chemokine (C-C motif) ligand 20 (CCL20), is emerging as a therapeutic target for immune-based therapies. Cooperative regulation of CCL20 by glucocorticoids and progestins used in endocrine therapy and pro-inflammatory mediators could modulate immune function and affect disease outcomes. We show that glucocorticoids as well as medroxyprogesterone acetate (MPA), the progestin widely used in injectable contraception in sub-Saharan Africa, cooperate with pro-inflammatory mediators to upregulate CCL20 protein and/or mRNA in human peripheral blood mononuclear cells (PBMCs) and human cervical cell lines. Changes in CCL20 mRNA levels were shown to be synergistic, as assessed by Chou analysis, cell- and gene-specific and to involve transcriptional regulation, with a requirement for a nuclear factor kappa B (NF-κB) site and glucocorticoid receptor (GR) involvement. The novel results suggest a mechanism whereby MPA, like glucocorticoids, may impact inflammation both systemically and in the genital tract in patients using MPA and/or glucocorticoid therapy.
Identifiants
pubmed: 36646303
pii: S0303-7207(23)00006-0
doi: 10.1016/j.mce.2023.111855
pmc: PMC9892260
mid: NIHMS1867193
pii:
doi:
Substances chimiques
Medroxyprogesterone Acetate
C2QI4IOI2G
Glucocorticoids
0
Progestins
0
Receptors, Glucocorticoid
0
RNA, Messenger
0
CCL20 protein, human
0
Chemokine CCL20
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
111855Subventions
Organisme : NIAID NIH HHS
ID : R01 AI152118
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD083026
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing interests.
Références
Infect Immun. 2003 Jan;71(1):365-73
pubmed: 12496186
J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):109-17
pubmed: 24413042
AIDS. 2018 Mar 13;32(5):595-604
pubmed: 29334545
Am J Reprod Immunol. 2014 Jun;71(6):505-12
pubmed: 24547700
Mol Endocrinol. 1998 Jan;12(1):45-56
pubmed: 9440809
J Immunol. 2002 Jun 1;168(11):5621-8
pubmed: 12023359
BMC Mol Biol. 2004 May 04;5:2
pubmed: 15125785
Mol Cell Endocrinol. 2009 Feb 27;299(2):219-31
pubmed: 19007848
Gastroenterology. 2009 Mar;136(3):933-42
pubmed: 19185581
PLoS Med. 2015 Jan 22;12(1):e1001778
pubmed: 25612136
AIDS Res Hum Retroviruses. 2015 Nov;31(11):1139-52
pubmed: 26204200
Sci Rep. 2019 Mar 13;9(1):4334
pubmed: 30867477
Int Immunol. 2002 Feb;14(2):147-55
pubmed: 11809734
PLoS One. 2018 Apr 26;13(4):e0196043
pubmed: 29698514
Genome Res. 2011 Sep;21(9):1404-16
pubmed: 21750107
AIDS. 2013 Jan 2;27(1):105-113
pubmed: 23014519
Nat Commun. 2015 Jan 14;6:6062
pubmed: 25585690
PLoS Pathog. 2022 May 9;18(5):e1010494
pubmed: 35533147
J Pharm Sci. 1991 Dec;80(12):1130-2
pubmed: 1839998
Comb Chem High Throughput Screen. 2011 May;14(4):248-66
pubmed: 21375502
mBio. 2015 Sep 01;6(5):e00221-15
pubmed: 26330510
Arch Gynecol. 1981;230(3):205-11
pubmed: 6787991
Reprod Biol Endocrinol. 2019 Feb 22;17(1):26
pubmed: 30795774
Mol Endocrinol. 2012 Mar;26(3):423-37
pubmed: 22240809
Biochemistry. 2010 Feb 9;49(5):972-85
pubmed: 20047289
PLoS One. 2019 Apr 4;14(4):e0213975
pubmed: 30947260
Pharmacol Ther. 2016 Sep;165:93-113
pubmed: 27288728
Mucosal Immunol. 2017 Mar;10(2):508-519
pubmed: 27435105
Mol Endocrinol. 2002 Jun;16(6):1269-79
pubmed: 12040014
Biol Reprod. 1997 Oct;57(4):847-55
pubmed: 9314589
AIDS. 2016 Nov 13;30(17):2665-2683
pubmed: 27500670
J Biol Chem. 1996 May 24;271(21):12568-77
pubmed: 8647867
Front Immunol. 2021 Feb 23;11:598307
pubmed: 33717049
Clin Infect Dis. 2020 Oct 23;71(7):e76-e87
pubmed: 31675420
J Biol Chem. 2014 Mar 21;289(12):8231-9
pubmed: 24500711
Endocr Rev. 2018 Feb 1;39(1):36-78
pubmed: 29309550
Endocrinology. 2012 Aug;153(8):3701-12
pubmed: 22673229
J Gen Virol. 2017 Mar;98(3):338-344
pubmed: 28005525
Blood. 2004 Jul 1;104(1):215-23
pubmed: 15031210
J Immunol. 2014 Feb 1;192(3):1196-208
pubmed: 24395918
Br J Cancer. 1988 Jul;58(1):73-6
pubmed: 2971386
Immunohorizons. 2017 Nov 1;1(9):223-235
pubmed: 29188238
Biol Reprod. 1999 Feb;60(2):508-14
pubmed: 9916021
AIDS Res Hum Retroviruses. 2019 Mar;35(3):236-246
pubmed: 30585733
Nat Commun. 2015 Jul 17;6:7796
pubmed: 26183376
Mol Cell Biol. 1990 Jun;10(6):2757-64
pubmed: 2111442
Sci Rep. 2017 Aug 29;7(1):9610
pubmed: 28851919
Steroids. 1975 Sep;26(3):373-86
pubmed: 1198624
J Infect Dis. 2000 Aug;182(2):467-73
pubmed: 10915077
Cancer Chemother Pharmacol. 2011 Sep;68(3):653-9
pubmed: 21125277
AIDS. 2020 Apr 1;34(5):729-735
pubmed: 31972606
J Biol Chem. 2002 May 10;277(19):17263-70
pubmed: 11867630
Front Immunol. 2016 Dec 19;7:604
pubmed: 28066415
Am J Reprod Immunol. 2022 Aug;88(2):e13542
pubmed: 35394678
J AIDS Clin Res. 2016 Jul;7(7):
pubmed: 27617163
Mol Cell Biol. 2004 Jun;24(11):4743-56
pubmed: 15143169
Clin Infect Dis. 2022 Nov 30;75(11):2000-2011
pubmed: 35941737
J Biol Chem. 2002 Dec 6;277(49):47444-50
pubmed: 12356755
J Infect Dis. 2019 Apr 8;219(8):1329-1337
pubmed: 30452655
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
Microbes Infect. 2014 Oct;16(10):864-70
pubmed: 25130722
J Biol Chem. 2017 Feb 3;292(5):1637-1647
pubmed: 27998979
PLoS One. 2015 Jun 09;10(6):e0129465
pubmed: 26057743
Lancet Infect Dis. 2015 Feb;15(2):181-9
pubmed: 25578825
Antimicrob Agents Chemother. 2019 Dec 20;64(1):
pubmed: 31658973
Cytokine Growth Factor Rev. 2010 Aug;21(4):275-86
pubmed: 20456998
Endocr Connect. 2017 Oct;6(7):500-509
pubmed: 28760748
Science. 2009 Mar 27;323(5922):1726-9
pubmed: 19325114
J Infect Dis. 2022 Apr 1;225(7):1151-1161
pubmed: 32780807
Mol Cell Biol. 1997 Jun;17(6):3181-93
pubmed: 9154817
J Invest Dermatol. 2009 Feb;129(2):375-82
pubmed: 18704103
PLoS One. 2012;7(3):e33419
pubmed: 22442690
J Steroid Biochem Mol Biol. 2014 Jul;142:39-47
pubmed: 23954501
Cancer Res. 2015 Dec 15;75(24):5248-59
pubmed: 26631268
J Biol Chem. 2016 Jun 10;291(24):12673-12687
pubmed: 27076634
PLoS One. 2014 May 19;9(5):e96497
pubmed: 24840644
Am J Pathol. 2012 Jul;181(1):8-18
pubmed: 22640807
AIDS Res Hum Retroviruses. 2011 Jun;27(6):655-7
pubmed: 21091320
J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):72-7
pubmed: 24025339
PLoS One. 2015 Mar 13;10(3):e0120855
pubmed: 25768730
ISRN Obstet Gynecol. 2012;2012:342075
pubmed: 22550593
J Pineal Res. 1986;3(3):263-75
pubmed: 3772725
J Steroid Biochem Mol Biol. 2012 Oct;132(1-2):66-72
pubmed: 22342838
J Biol Chem. 2017 Apr 28;292(17):7163-7172
pubmed: 28283576
Mol Cell Biol. 2012 Feb;32(4):730-9
pubmed: 22158970
Endocr Rev. 2013 Apr;34(2):171-208
pubmed: 23238854
Eur Respir J. 2014 Aug;44(2):361-70
pubmed: 24627531
Issues Law Med. 2015 Autumn;30(2):129-39
pubmed: 26710371
Obstet Gynecol. 1997 Feb;89(2):276-80
pubmed: 9015035
PLoS One. 2013 May 03;8(5):e62895
pubmed: 23658782
Am J Reprod Immunol. 2018 Jan;79(1):
pubmed: 29105931