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Inflammation Research
Erschienen in: Inflammation Research 7/2023

16.06.2023 | Original Research Paper

Loss of TRIM24 promotes IL-10 expression via CBP/p300-dependent IFNβ1 transcription during macrophage activation

verfasst von: Zhaoyuan Hui, Yuanzheng Fu, Yunyun Chen, Jie Yin, Hui Fang, Yifan Tu, Ying Gu, Jiawei Zhang

Erschienen in: Inflammation Research | Ausgabe 7/2023

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Abstract

Background

As an anti-inflammatory cytokine, interleukin 10 (IL-10) plays a vital role in preventing inflammatory and autoimmune pathologies while also maintaining immune homeostasis. IL-10 production in macrophages is tightly regulated by multiple pathways. TRIM24, a member of the Transcriptional Intermediary Factor 1 (TIF1) family, contributes to antiviral immunity and macrophage M2 polarization. However, the role of TRIM24 in regulating IL-10 expression and its involvement in endotoxic shock remains unclear.

Methods

In vitro, bone marrow derived macrophages cultured with GM-CSF or M-CSF were stimulated with LPS (100ng/ml). Murine models of endotoxic shock were established by challenging the mice with different dose of LPS (i.p). RTPCR, RNA sequencing, ELISA and hematoxylin and eosin staining were performed to elucidate the role and mechanisms of TRIM24 in endotoxic shock.

Results

The expression of TRIM24 is downregulated in LPS-stimulated bone marrow-derived macrophages (BMDMs). Loss of TRIM24 boosted IL-10 expression during the late stage of LPS-stimulation in macrophages. RNA-seq analysis revealed the upregulation of IFNβ1, an upstream regulator of IL-10, in TRIM24 knockout macrophages. Treatment with C646, a CBP/p300 inhibitor, diminished the difference in both IFNβ1 and IL-10 expression between TRIM24 knockout and control macrophages. Loss of TRIM24 provided protection against LPS-induced endotoxic shock in mice.

Conclusion

Our results demonstrated that inhibiting TRIM24 promoted the expression of IFNβ1 and IL-10 during macrophage activation, therefore protecting mice from endotoxic shock. This study offers novel insights into the regulatory role of TRIM24 in IL-10 expression, making it a potentially attractive therapeutic target for inflammatory diseases.
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Literatur
1.
2.
3.
Murray Peter J, Allen Judith E, Biswas Subhra K, Fisher Edward A, Gilroy Derek W, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14–20.PubMedPubMedCentralCrossRef
4.
Wenjun O, Anne O. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 2019.
5.
Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28:546–58.PubMedCrossRef
6.
Na YR, Stakenborg M, Seok SH, Matteoli G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol. 2019;16:531–43.PubMedCrossRef
7.
Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–74.PubMedCrossRef
8.
Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10:170–81.PubMedCrossRef
9.
Yoo C-H, Yeom J-H, Heo J-J, Song E-K, Lee S-I, Han M-K. Interferon β protects against lethal endotoxic and septic shock through SIRT1 upregulation. Sci Rep. 2014;4:4220–4220.PubMedPubMedCentralCrossRef
10.
Howes A, Taubert C, Blankley S, Spink N, Wu X, Graham CM, et al. Differential production of type I IFN determines the reciprocal levels of IL-10 and proinflammatory cytokines produced by C57BL/6 and BALB/c macrophages. J Immunol. 2016;197:2838–53.PubMedPubMedCentralCrossRef
11.
12.
Herquel B, Ouararhni K, Davidson I. The TIF1α-related TRIM cofactors couple chromatin modifications to transcriptional regulation, signaling and tumor suppression. Transcription. 2011;2:231–6.PubMedPubMedCentralCrossRef
13.
Zhu Q, Yu T, Gan S, Wang Y, Pei Y, Zhao Q, et al. TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination. J Exp Med. 2020;217:2.CrossRef
14.
Yu T, Gan S, Zhu Q, Dai D, Li N, Wang H, et al. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. Nat Commun. 2019;10:4353.PubMedPubMedCentralCrossRef
15.
McAvera RM, Crawford LJ. TIF1 proteins in genome stability and cancer. Cancers (Basel). 2020;12:2.CrossRef
16.
Jiang S, Minter LC, Stratton SA, Yang P, Abbas HA, Akdemir ZC, et al. TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice. J Hepatol. 2015;62:371–9.PubMedCrossRef
17.
Hui Z, Zhou L, Xue Z, Zhou L, Luo Y, Lin F, et al. Cxxc finger protein 1 positively regulates GM-CSF-derived macrophage phagocytosis through Csf2ralpha-mediated signaling. Front Immunol. 2018;9:1885.PubMedPubMedCentralCrossRef
18.
Zhang X, Goncalves R, Mosser DM. The isolation and characterization of murine macrophages. Curr Protoc Immunol 2008; Chapter 14: 14.1
19.
Li R, Li Y, Kristiansen K, Wang J. SOAP: short oligonucleotide alignment program. Bioinformatics. 2008;24:713–4.PubMedCrossRef
20.
21.
22.
Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 2011;12:323.CrossRef
23.
Yang W, Gu Z, Zhang H, Hu H. To TRIM the immunity: from innate to adaptive immunity. Front Immunol. 2020;11:2.CrossRef
24.
Ferri F, Parcelier A, Petit V, Gallouet A-S, Lewandowski D, Dalloz M, et al. TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation. Nat Commun. 2015;6:8900.PubMedCrossRef
25.
Merika M, Williams AJ, Chen G, Collins T, Thanos D. Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. Mol Cell. 1998;1:277–87.PubMedCrossRef
26.
Berg DJ, Kühn R, Rajewsky K, Müller W, Menon S, Davidson N, et al. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J Clin Investig. 1995;96:2339–47.PubMedPubMedCentralCrossRef
27.
Zigmond E, Bernshtein B, Friedlander G, Walker Catherine R, Yona S, Kim K-W, et al. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency causes severe spontaneous colitis. Immunity. 2014;40:720–33.PubMedCrossRef
28.
Shemer A, Scheyltjens I, Frumer GR, Kim J-S, Grozovski J, Ayanaw S, et al. Interleukin-10 prevents pathological microglia hyperactivation following peripheral endotoxin challenge. Immunity. 2020;53:1033-1049.e7.PubMedCrossRef
29.
Ip WKE, Hoshi N, Shouval DS, Snapper SB, Medzhitov R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science. 2017;356:513–9.PubMedPubMedCentralCrossRef
30.
Kumaran Satyanarayanan S, El Kebir D, Soboh S, Butenko S, Sekheri M, Saadi J, et al. IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation. Nat Commun. 2019;10:3471.PubMedPubMedCentralCrossRef
31.
Khetchoumian K, Teletin M, Tisserand J, Mark M, Herquel B, Ignat M, et al. Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha. Nat Genet. 2007;39:1500–6.PubMedCrossRef
32.
Herquel B, Ouararhni K, Khetchoumian K, Ignat M, Teletin M, Mark M, et al. Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2011;108:8212–7.PubMedPubMedCentralCrossRef
33.
Groner AC, Cato L, de Tribolet-Hardy J, Bernasocchi T, Janouskova H, Melchers D, et al. TRIM24 is an oncogenic transcriptional activator in prostate cancer. Cancer Cell. 2016;29:846–58.PubMedPubMedCentralCrossRef
34.
Perez-Lloret J, Okoye IS, Guidi R, Kannan Y, Coomes SM, Czieso S, et al. T-cell-intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy. Proc Natl Acad Sci U S A. 2016;113:E568–76.PubMedPubMedCentralCrossRef
35.
Okoye IS, Czieso S, Ktistaki E, Roderick K, Coomes SM, Pelly VS, et al. Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity. Proc Natl Acad Sci U S A. 2014;111:E3081–90.PubMedPubMedCentralCrossRef
36.
Buscher K, Ehinger E, Gupta P, Pramod AB, Wolf D, Tweet G, et al. Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival. Nat Commun. 2017;8:16041.PubMedPubMedCentralCrossRef
37.
Abdelaziz MH, Abdelwahab SF, Wan J, Cai W, Huixuan W, Jianjun C, et al. Alternatively activated macrophages; a double-edged sword in allergic asthma. J Transl Med. 2020;18:58.PubMedPubMedCentralCrossRef
38.
Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog. 2009;5: e1000371.PubMedPubMedCentralCrossRef
39.
Yurdagul A Jr, Subramanian M, Wang X, Crown SB, Ilkayeva OR, Darville L, et al. Macrophage metabolism of apoptotic cell-derived arginine promotes continual efferocytosis and resolution of injury. Cell Metab. 2020;31:518-533.e10.PubMedPubMedCentralCrossRef
40.
Duque-Correa MA, Kühl AA, Rodriguez PC, Zedler U, Schommer-Leitner S, Rao M, et al. Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas. Proc Natl Acad Sci. 2014;111:E4024–32.PubMedPubMedCentralCrossRef
41.
Duleu S, Vincendeau P, Courtois P, Semballa S, Lagroye I, Daulouède S, et al. Mouse strain susceptibility to trypanosome infection: an arginase-dependent effect. J Immunol. 2004;172:6298–303.PubMedCrossRef
42.
Abebe T, Hailu A, Woldeyes M, Mekonen W, Bilcha K, Cloke T, et al. Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in Ethiopia. PLoS Negl Trop Dis. 2012;6: e1684.PubMedPubMedCentralCrossRef
43.
El Kasmi KC, Qualls JE, Pesce JT, Smith AM, Thompson RW, Henao-Tamayo M, et al. Toll-like receptor–induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat Immunol. 2008;9:1399–406.PubMedPubMedCentralCrossRef
44.
Lerchenmüller C, Rabolli CP, Yeri A, Kitchen R, Salvador AM, Liu LX, et al. CITED4 protects against adverse remodeling in response to physiological and pathological stress. Circ Res. 2020;127:631–46.PubMedPubMedCentral
45.
Lee H, Park S, Kong G, Kwon SH, Park J, Park J, et al. Phosphodiesterase 11 A (PDE11A), a potential biomarker for glioblastoma. Toxicol Res. 2022;38:409–15.PubMedPubMedCentralCrossRef
46.
47.
Xu H, Ma G, Mu F, Ning B, Li H, Wang N. STAT3 partly inhibits cell proliferation via direct negative regulation of FST gene expression. Front Genet. 2021;12:2.
48.
49.
50.
Margalit L, Strauss C, Tal A, Schlesinger S. Trim24 and Trim33 play a role in epigenetic silencing of retroviruses in embryonic stem cells. Viruses. 2020;12:1015.PubMedPubMedCentralCrossRef
Metadaten
Titel
Loss of TRIM24 promotes IL-10 expression via CBP/p300-dependent IFNβ1 transcription during macrophage activation
verfasst von
Zhaoyuan Hui
Yuanzheng Fu
Yunyun Chen
Jie Yin
Hui Fang
Yifan Tu
Ying Gu
Jiawei Zhang
Publikationsdatum
16.06.2023
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 7/2023
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-023-01751-x

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