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Protein C-ets-2 epigenetically suppresses TLRs-induced interleukin 6 production in macrophages.

Abstract

Interleukin 6 (IL-6) is a major proinflammatory cytokine involved in several aspects of the immune response. Excessive IL-6 production and dysregulated IL-6 receptor signaling lead to multiple inflammatory and autoimmune diseases, such as asthma, even cancer. Thus, its precise regulatory mechanisms need to be fully addressed. Here we found that knockdown of protein C-ets-2 (Ets2) resulted in higher IL-6 production after TLRs activation in macrophages. Mechanistically, Ets2 associated with an epigenetic modifier histone deacetylase 1 (HDAC1) and promoted its recruitment to the Il6 promoter after TLRs activation. Subsequentially, it enhanced histone deacetylation and inhibited Il6 mRNA transcription. Thus, Ets2 epigenetically suppresses TLRs-induced IL-6 production in both human and murine macrophages via promoting histone deacetylation of the Il6 promoter, serving as a new potential therapeutic target in inflammatory diseases therapy.

Authors+Show Affiliations

Department of Respiration, Zhejiang Medical & Health Group Hangzhou Hospital, 1 Banshan Road, Hangzhou, 310022, Zhejiang, China. Electronic address: zhaojun_hangzhou@sina.com.Department of Laboratory Diagnosis, NO.425 Hospital, 86 Sanyawan Road, Sanya, 572000, Hainan, China. Electronic address: 13564525932@163.com.Department of Respiration, Zhejiang Medical & Health Group Hangzhou Hospital, 1 Banshan Road, Hangzhou, 310022, Zhejiang, China. Electronic address: 13588133122@sina.com.Department of Laboratory Diagnosis, NO.425 Hospital, 86 Sanyawan Road, Sanya, 572000, Hainan, China. Electronic address: fengjifeng2007@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31810605

Citation

Zhao, Jun, et al. "Protein C-ets-2 Epigenetically Suppresses TLRs-induced Interleukin 6 production in Macrophages." Biochemical and Biophysical Research Communications, 2019.
Zhao J, Huang K, Peng HZ, et al. Protein C-ets-2 epigenetically suppresses TLRs-induced interleukin 6 production in macrophages. Biochem Biophys Res Commun. 2019.
Zhao, J., Huang, K., Peng, H. Z., & Feng, J. F. (2019). Protein C-ets-2 epigenetically suppresses TLRs-induced interleukin 6 production in macrophages. Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2019.11.123.
Zhao J, et al. Protein C-ets-2 Epigenetically Suppresses TLRs-induced Interleukin 6 production in Macrophages. Biochem Biophys Res Commun. 2019 Dec 3; PubMed PMID: 31810605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein C-ets-2 epigenetically suppresses TLRs-induced interleukin 6 production in macrophages. AU - Zhao,Jun, AU - Huang,Kai, AU - Peng,Hui-Zhong, AU - Feng,Ji-Feng, Y1 - 2019/12/03/ PY - 2019/10/22/received PY - 2019/11/19/accepted PY - 2019/12/8/entrez PY - 2019/12/8/pubmed PY - 2019/12/8/medline KW - Epigenetics KW - HDAC1/2 KW - Histone acetylation KW - Interleukin 6 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. N2 - Interleukin 6 (IL-6) is a major proinflammatory cytokine involved in several aspects of the immune response. Excessive IL-6 production and dysregulated IL-6 receptor signaling lead to multiple inflammatory and autoimmune diseases, such as asthma, even cancer. Thus, its precise regulatory mechanisms need to be fully addressed. Here we found that knockdown of protein C-ets-2 (Ets2) resulted in higher IL-6 production after TLRs activation in macrophages. Mechanistically, Ets2 associated with an epigenetic modifier histone deacetylase 1 (HDAC1) and promoted its recruitment to the Il6 promoter after TLRs activation. Subsequentially, it enhanced histone deacetylation and inhibited Il6 mRNA transcription. Thus, Ets2 epigenetically suppresses TLRs-induced IL-6 production in both human and murine macrophages via promoting histone deacetylation of the Il6 promoter, serving as a new potential therapeutic target in inflammatory diseases therapy. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31810605/Protein_C-ets-2_epigenetically_suppresses_TLRs-induced_interleukin_6 production_in_macrophages L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)32251-X DB - PRIME DP - Unbound Medicine ER -