The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
BET Protein Function Is Required for Inflammation: Brd2 Genetic Disruption and BET Inhibitor JQ1 Impair Mouse Macrophage Inflammatory Responses
Open accessAbstract
Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated proinflammatory cytokine response remain poorly characterized. Bromodomain and extraterminal (BET) proteins are “readers” of histone acetylation marks, with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for proinflammatory cytokine production in macrophages. Studies that use small interfering RNA knockdown and a small-molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the “cytokine storm” in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small-molecule inhibitors will benefit hyperinflammatory conditions associated with high levels of cytokine production.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Interferon-γ: an overview of signals, mechanisms and functions
Schroder, K., Hertzog, P. J., Ravasi, T., & Hume, D. A. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0603252 · Cited by 4,120
M-1/M-2 Macrophages and the Th1/Th2 Paradigm
Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., & Hill, A. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6166 · Cited by 3,287
Structure and ligand of a histone acetyltransferase bromodomain
Dhalluin, C., Carlson, J. E., Zeng, L., He, C., Aggarwal, A. K., Zhou, M.-M., & Zhou, M.-M. (1999) · Nature · doi:10.1038/20974 · Cited by 1,732
Suppression of inflammation by a synthetic histone mimic
Nicodeme, E., Jeffrey, K. L., Schaefer, U., Beinke, S., Dewell, S., Chung, C.-W., Chandwani, R., Marazzi, I., Wilson, P., Coste, H., et al. (2010) · Nature · doi:10.1038/nature09589 · Cited by 1,563
Houzelstein, D., Bullock, S. L., Lynch, D. E., Grigorieva, E. F., Wilson, V. A., & Beddington, R. S. P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.11.3794-3802.2002 · Cited by 318
Brd2 disruption in mice causes severe obesity without Type 2 diabetes
Wang, F., Liu, H., Blanton, W. P., Belkina, A., Lebrasseur, N. K., & Denis, G. V. (2010) · Biochemical Journal · doi:10.1042/bj20090928 · Cited by 185
Self-citationDouble bromodomain‐containing gene Brd2 is essential for embryonic development in mouse
Shang, E., Wang, X., Wen, D., Greenberg, D. A., & Wolgemuth, D. J. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21911 · Cited by 156
Cited by
Targeting bromodomains: epigenetic readers of lysine acetylation
Filippakopoulos, P., & Knapp, S. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4286 · Cited by 1,243
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415
“Besides their novel role in senescence surveillance as described above, BET proteins are crucial for the inflammatory response of various immune cells (41, 58).”
BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression
Zhu, H., Bengsch, F., Svoronos, N., Rutkowski, M. R., Bitler, B. G., Allegrezza, M. J., Yokoyama, Y., Kossenkov, A. V., Bradner, J. E., Conejo-Garcia, J. R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.032 · Cited by 432
A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors
Wang, T., Wang, D., Yu, H., Feng, B., Zhou, F., Zhang, H., Zhou, L., Jiao, S., & Li, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-03915-4 · Cited by 391
Molecular and epigenetic basis of macrophage polarized activation
Porta, C., Riboldi, E., Ippolito, A., & Sica, A. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.10.003 · Cited by 320
Metadata
- Authors
- Belkina, A. C., Nikolajczyk, B. S., & Denis, G. V.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04-01
- Volume
- 190
- Issue
- 7
- Pages
- 3670-3678
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2150469988
- Cited by
- 418
- References
- 10
- FWCI
- 15.47
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: BET Protein Function Is Required for Inflammation: Brd2 Genetic Disruption and BET Inhibitor JQ1 Impair Mouse Macrophage Inflammatory Responses. https://app.cochat.ai/papers/10.4049/jimmunol.1202838
- The paper
- Belkina, A. C., Nikolajczyk, B. S., & Denis, G. V. (2013). BET Protein Function Is Required for Inflammation: Brd2 Genetic Disruption and BET Inhibitor JQ1 Impair Mouse Macrophage Inflammatory Responses. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1202838
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
