High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors.

Szczegóły
Abstrakt

Tytuł:: High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors.
Autorzy:: Ullmann T; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Luckhardt S; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Wolf M; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany.
Parnham MJ; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.; EpiEndo Pharmaceuticals ehf, Eiðistorg 13-15, 170 Seltjarnarnes, Iceland.
Resch E; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2021 Mar 16; Vol. 22 (6). Date of Electronic Publication: 2021 Mar 16.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Genes, Reporter*
High-Throughput Screening Assays*
Anti-Inflammatory Agents/*pharmacology
CCAAT-Enhancer-Binding Protein-delta/*metabolism
Histone Deacetylase Inhibitors/*pharmacology
Macrophages/*metabolism
Alkaline Phosphatase/metabolism ; Azepines/pharmacology ; CCAAT-Enhancer-Binding Protein-delta/antagonists & inhibitors ; Gene Expression Regulation/drug effects ; HEK293 Cells ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Hydroxamic Acids/pharmacology ; Luminescent Measurements ; Macrophages/drug effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; THP-1 Cells ; Thiophenes/pharmacology ; Vorinostat/pharmacology
References:: J Cell Biochem. 2007 Dec 1;102(5):1256-70. (PMID: 17471507)
Biochim Biophys Acta Gene Regul Mech. 2018 May 18;:. (PMID: 29778644)
Genomics. 1998 Aug 15;52(1):1-8. (PMID: 9740665)
Nat Rev Cancer. 2012 Jun 22;12(7):465-77. (PMID: 22722403)
Nat Rev Drug Discov. 2014 Sep;13(9):673-91. (PMID: 25131830)
Cardiovasc Res. 2011 Jul 1;91(1):90-8. (PMID: 21382976)
Int J Mol Sci. 2020 Nov 25;21(23):. (PMID: 33255670)
J Inflamm Res. 2016 Feb 09;9:1-11. (PMID: 26929657)
J Biol Chem. 2003 Jul 18;278(29):26612-9. (PMID: 12736252)
Int J Mol Sci. 2018 Jul 24;19(8):. (PMID: 30042333)
Biomed Res Int. 2016;2016:8797206. (PMID: 27556043)
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10193-7. (PMID: 8234276)
Clin Cancer Res. 2001 Apr;7(4):971-6. (PMID: 11309348)
Arch Pharm Res. 2009 Apr;32(4):613-24. (PMID: 19407980)
FASEB J. 2006 Jul;20(9):1315-27. (PMID: 16816106)
Gene. 1988 Jun 15;66(1):1-10. (PMID: 3417148)
Nat Commun. 2013;4:1662. (PMID: 23575666)
Rheumatology (Oxford). 2010 Aug;49(8):1447-60. (PMID: 20421217)
Sheng Li Xue Bao. 2012 Dec 25;64(6):651-6. (PMID: 23258328)
BMC Mol Biol. 2010 Dec 01;11:90. (PMID: 21122122)
PLoS One. 2012;7(9):e45378. (PMID: 23028973)
Int J Mol Sci. 2019 Mar 05;20(5):. (PMID: 30841513)
Biochem J. 2002 Aug 1;365(Pt 3):561-75. (PMID: 12006103)
Genes Dev. 1988 Jul;2(7):786-800. (PMID: 2850264)
Prostate. 2005 May 1;63(2):143-54. (PMID: 15486993)
Int J Mol Sci. 2020 Nov 03;21(21):. (PMID: 33153042)
J Biochem. 1997 Apr;121(4):731-8. (PMID: 9163525)
Cell Signal. 2006 Sep;18(9):1492-500. (PMID: 16413748)
Methods Enzymol. 1992;216:362-8. (PMID: 1479908)
Cell Mol Life Sci. 2007 Dec;64(24):3282-94. (PMID: 17965828)
EMBO J. 2010 Dec 15;29(24):4106-17. (PMID: 21076392)
J Biol Chem. 2012 Jul 27;287(31):25844-59. (PMID: 22679019)
Prog Neurobiol. 2015 Sep;132:1-33. (PMID: 26143335)
Oncologist. 2007 Oct;12(10):1247-52. (PMID: 17962618)
Ann Rheum Dis. 2016 Feb;75(2):422-9. (PMID: 25467295)
Sci Signal. 2013 Jul 16;6(284):ra59. (PMID: 23861541)
Nat Immunol. 2009 Apr;10(4):437-43. (PMID: 19270711)
Int J Biol Sci. 2013 Sep 20;9(9):917-33. (PMID: 24155666)
Am J Pathol. 2013 Feb;182(2):420-30. (PMID: 23177475)
J Immunol. 1998 Mar 1;160(5):2334-42. (PMID: 9498774)
Pharmacol Ther. 2016 Jan;157:163-87. (PMID: 26627986)
Curr Med Chem. 2016;23(18):1926-37. (PMID: 27121189)
Biochim Biophys Acta. 2014 Sep;1842(9):1549-55. (PMID: 24859008)
Int J Biochem Cell Biol. 2010 Jan;42(1):113-9. (PMID: 19800021)
Int J Mol Sci. 2016 Nov 07;17(11):. (PMID: 27827996)
Int J Med Sci. 2019 Jan 29;16(3):424-442. (PMID: 30911277)
Sci Rep. 2015 Jul 13;5:12132. (PMID: 26166618)
J Biol Chem. 2005 Mar 25;280(12):11432-8. (PMID: 15644333)
J Immunol. 2009 Jun 1;182(11):7212-21. (PMID: 19454718)
J Immunol. 2013 Apr 1;190(7):3670-8. (PMID: 23420887)
Immunol Cell Biol. 2021 Feb;99(2):122-125. (PMID: 33179321)
Immunol Rev. 2021 Jan;299(1):45-60. (PMID: 33107072)
Nat Rev Rheumatol. 2020 Dec;16(12):673-688. (PMID: 33122845)
Science. 2001 Aug 31;293(5535):1653-7. (PMID: 11533489)
Curr Drug Targets. 2012 Jul;13(8):1029-47. (PMID: 22594471)
Mol Endocrinol. 2003 Sep;17(9):1834-43. (PMID: 12791769)
Nucleic Acids Res. 2008 Nov;36(19):6066-79. (PMID: 18820298)
J Med Chem. 2011 Oct 13;54(19):6761-70. (PMID: 21851057)
Cell. 1991 Nov 1;67(3):569-79. (PMID: 1934061)
J Biol Chem. 2002 Jun 28;277(26):23563-72. (PMID: 11980905)
J Biol Chem. 1992 Mar 15;267(8):5021-4. (PMID: 1371993)
J Biol Chem. 1996 Jul 26;271(30):17974-8. (PMID: 8663327)
Neurobiol Aging. 2012 Feb;33(2):422.e11-25. (PMID: 21112127)
Gene. 2002 Jan 9;282(1-2):19-31. (PMID: 11814674)
J Immunol. 2001 Nov 1;167(9):5160-6. (PMID: 11673528)
Genes Dev. 1992 Mar;6(3):439-53. (PMID: 1547942)
Neurobiol Aging. 2014 Jan;35(1):24-34. (PMID: 23993701)
Bioorg Med Chem Lett. 2012 Apr 15;22(8):2968-72. (PMID: 22437115)
Mol Med Rep. 2016 Jan;13(1):845-52. (PMID: 26647731)
J Biol Chem. 2003 Jan 24;278(4):2758-66. (PMID: 12419806)
J Cell Physiol. 2005 Jul;204(1):219-26. (PMID: 15669083)
J Biol Chem. 1994 Jul 22;269(29):19041-7. (PMID: 8034662)
J Biol Chem. 1998 Nov 6;273(45):29279-82. (PMID: 9792624)
Genes Dev. 1991 Sep;5(9):1538-52. (PMID: 1840554)
Sci Rep. 2019 Sep 27;9(1):13953. (PMID: 31562350)
Glia. 2000 Jan 1;29(1):91-7. (PMID: 10594926)
Mol Immunol. 2017 Aug;88:58-68. (PMID: 28600970)
Nature. 2010 Dec 23;468(7327):1119-23. (PMID: 21068722)
J Biol Chem. 2003 Mar 28;278(13):11246-55. (PMID: 12554732)
Nat Rev Immunol. 2009 Oct;9(10):692-703. (PMID: 19859064)
Front Immunol. 2019 Apr 30;10:933. (PMID: 31114581)
Cytokine. 2000 Sep;12(9):1430-6. (PMID: 10976009)
Cytokine. 2011 Apr;54(1):6-19. (PMID: 21257317)
J Biomed Sci. 2015 Jan 16;22:6. (PMID: 25591788)
Nat Chem Biol. 2013 May;9(5):319-25. (PMID: 23524983)
Bosn J Basic Med Sci. 2021 Apr 01;21(2):155-162. (PMID: 32937098)
Int J Mol Sci. 2019 Jan 16;20(2):. (PMID: 30654448)
Anal Biochem. 1999 Jul 1;271(2):187-9. (PMID: 10419635)
J Cell Biochem. 2004 Nov 1;93(4):844-56. (PMID: 15389878)
Nature. 2011 May 19;473(7347):317-25. (PMID: 21593864)
PLoS One. 2012;7(2):e31062. (PMID: 22347430)
Lipid Insights. 2013 Dec 22;6:47-54. (PMID: 25278768)
Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1773-8. (PMID: 20702809)
Am J Respir Crit Care Med. 2007 Sep 15;176(6):602-9. (PMID: 17600275)
Cancers (Basel). 2019 Aug 01;11(8):. (PMID: 31374929)
J Biomed Sci. 2007 May;14(3):407-18. (PMID: 17273900)
Mol Cell Biol. 1998 Apr;18(4):2108-17. (PMID: 9528783)
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1503-8. (PMID: 11805289)
Eur J Immunol. 2015 Jan;45(1):287-297. (PMID: 25345375)
Database (Oxford). 2016 Jul 03;2016:. (PMID: 27374120)
J Immunol. 2013 Jun 15;190(12):6542-9. (PMID: 23667114)
Biochim Biophys Acta. 2000 Jun 15;1501(2-3):171-9. (PMID: 10838190)
J Biomol Screen. 2007 Mar;12(2):229-34. (PMID: 17218666)
Nucleic Acids Res. 2006 Jan 05;34(1):217-31. (PMID: 16397300)
Gene. 2005 Dec 19;363:15-23. (PMID: 16289629)
Science. 2005 Jan 14;307(5707):269-73. (PMID: 15653507)
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):972-7. (PMID: 11805339)
Atherosclerosis. 1998 Jul;139(1):147-52. (PMID: 9699902)
Biochem Pharmacol. 2020 Oct;180:114147. (PMID: 32653589)
FASEB J. 2012 May;26(5):2019-30. (PMID: 22271762)
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1473-6. (PMID: 1741402)
Nat Rev Drug Discov. 2014 May;13(5):337-56. (PMID: 24751816)
J Pharmacol Exp Ther. 2016 Feb;356(2):387-96. (PMID: 26660228)
Bioorg Med Chem Lett. 2012 Apr 15;22(8):2963-7. (PMID: 22386529)
Int J Mol Sci. 2017 Jul 01;18(7):. (PMID: 28671573)
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2995-3000. (PMID: 11867742)
Life Sci Alliance. 2018 Sep 24;1(5):e201800039. (PMID: 30456376)
Clin Chim Acta. 2020 Jun;505:55-59. (PMID: 32092318)
J Immunol. 2011 Apr 1;186(7):4467-73. (PMID: 21357541)
Contributed Indexing:: Keywords: CEBPD; I-BET151; Ro 11-1464; SAHA; SEAP; TSA; anti-inflammatory drug; phenotypic screening
Substance Nomenclature:: 0 (9-methyl-4-phenyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine)
0 (Anti-Inflammatory Agents)
0 (Azepines)
0 (CEBPD protein, human)
0 (GSK1210151A)
0 (Heterocyclic Compounds, 4 or More Rings)
0 (Histone Deacetylase Inhibitors)
0 (Hydroxamic Acids)
0 (RNA, Messenger)
0 (Thiophenes)
142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
3X2S926L3Z (trichostatin A)
58IFB293JI (Vorinostat)
EC 3.1.3.1 (Alkaline Phosphatase)
Entry Date(s):: Date Created: 20210403 Date Completed: 20210422 Latest Revision: 20210422
Update Code:: 20240105
PubMed Central ID:: PMC8002291
DOI:: 10.3390/ijms22063022
PMID:: 33809617
: Czasopismo naukowe

Full Text Finder

This study aimed to identify alternative anti-inflammatory compounds that modulate the activity of a relevant transcription factor, CCAAT/enhancer binding protein delta (C/EBPδ). C/EBPδ is a master regulator of inflammatory responses in macrophages (Mϕ) and is mainly regulated at the level of CEBPD gene transcription initiation. To screen for CEBPD -modulating compounds, we generated a THP-1-derived reporter cell line stably expressing secreted alkaline phosphatase (SEAP) under control of the defined CEBPD promoter ( CEBPD::SEAP ). A high-throughput screening of LOPAC ®1280 and ENZO ®774 libraries on LPS- and IFN-γ-activated THP-1 reporter Mϕ identified four epigenetically active hits: two bromodomain and extraterminal domain (BET) inhibitors, I-BET151 and Ro 11-1464, as well as two histone deacetylase (HDAC) inhibitors, SAHA and TSA. All four hits markedly and reproducibly upregulated SEAP secretion and CEBPD::SEAP mRNA expression, confirming screening assay reliability. Whereas BET inhibitors also upregulated the mRNA expression of the endogenous CEBPD , HDAC inhibitors completely abolished it. All hits displayed anti-inflammatory activity through the suppression of IL-6 and CCL2 gene expression. However, I-BET151 and HDAC inhibitors simultaneously upregulated the mRNA expression of pro-inflammatory IL-1ß . The modulation of CEBPD gene expression shown in this study contributes to our understanding of inflammatory responses in Mϕ and may offer an approach to therapy for inflammation-driven disorders.

Informacja