Research Paper Volume 11, Issue 22 pp 10610—10625
Ets2 suppresses inflammatory cytokines through MAPK/NF-κB signaling and directly binds to the IL-6 promoter in macrophages
- 1 Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- 2 Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
- 3 Department of Respiration, Second Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- 4 Cancer Institute, Institute of Translational Medicine, Second Military Medical University/Naval Medical University, Shanghai 200433, China
- 5 National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University/Naval Medical University, Shanghai 200433, China
- 6 Department of Respiratory Diseases, Huashan Hospital, Fudan University, Shanghai 200433, China
received: August 15, 2019 ; accepted: November 8, 2019 ; published: November 27, 2019 ;https://doi.org/10.18632/aging.102480
How to Cite
Copyright © 2019 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Proper activation of Toll-like receptor (TLR)-mediated signaling and production of proinflammatory cytokines are critical for the initiation of innate immunity, while the specific mechanism maintaining inflammatory homeostasis remains mostly unknown. Here, we show that Ets2 is upregulated following LPS and VSV stimulation. Ets2 knockdown or knockout leads to increased IL-6, TNF-α, and IFN-β production in macrophages. Consistently, Ets2-deficient mice show exacerbated inflammatory cytokine production and are more susceptible to CLP-induced sepsis. Mechanistically, Ets2 inhibits the LPS- and VSV-induced activation of ERK1/2, JNK, p38, and p65. Ets2 also binds to the promoter of IL-6 to inhibit transcription. Collectively, the results of the present study show the negative regulatory role of Ets2 in LPS- and VSV-induced inflammation through the suppression of MAPK/NF-κB signaling, direct binding to the IL-6 promoter and inhibition of transcription.
TLR: Toll-like receptor; MyD88: myeloid differentiation factor 88; TRIF: Toll/IL-1 receptor domain-containing adapter inducing interferon-β; Ets2: V-ets erythroblastosis virus E26 oncogene homolog 2; CLP: cecal ligation and puncture.