PMID- 33615540 OWN - NLM STAT- MEDLINE DCOM- 20210505 LR - 20240226 IS - 1938-3673 (Electronic) IS - 0741-5400 (Linking) VI - 109 IP - 5 DP - 2021 May TI - Frontline Science: Estrogen-related receptor gamma increases poly(I:C)-mediated type I IFN expression in mouse macrophages. PG - 865-875 LID - 10.1002/JLB.2HI1219-762R [doi] AB - Although type I IFNs (IFN-I) are important for the innate and adaptive immune responses to suppress viral replication, prolonged IFN-I signaling in macrophages suppresses the immune response. Nuclear receptor estrogen-related receptor gamma (ERRgamma) regulates the transcription of genes involved in endocrine and metabolic functions. However, the role of ERRgamma in macrophage immune responses to viruses remains largely unknown. ERRgamma expression was significantly induced in mouse bone marrow-derived macrophages (BMDMs) treated with polyinosinic-polycytidylic acid (poly(I:C)). Our results indicated that the induction of ERRgamma expression by poly(I:C) is mediated through activation of the cytoplasmic dsRNA receptors, retinoic acid-inducible gene I and melanoma differentiation-associated protein 5. In BMDMs, overexpression of ERRgamma significantly increased gene expression and secretion of the IFN-I genes, IFN-alpha and IFN-beta, whereas abolition of ERRgamma significantly attenuated poly(I:C)-mediated IFN-I secretion. Chromatin immunoprecipitation assays and mutation analyses of the IFN-I promoters revealed that ERRgamma regulates the transcription of IFN-alpha and IFN-beta by binding to a conserved ERR response element in each promoter region. Finally, GSK5182 significantly suppressed poly(I:C)-mediated induction of IFN-I gene expression and secretion in BMDMs. Taken together, these findings reveal a previously unrecognized role for ERRgamma in the transcriptional control of innate and adaptive immune response to dsRNA virus replication. CI - (c)2020 Society for Leukocyte Biology. FAU - Kim, Ki-Sun AU - Kim KS AD - National Creative Research Initiatives Center for Nuclear Receptor Signals, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. FAU - Kim, Don-Kyu AU - Kim DK AD - Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, Republic of Korea. FAU - Na, Soon-Young AU - Na SY AD - National Creative Research Initiatives Center for Nuclear Receptor Signals, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. FAU - Jung, Yoon Seok AU - Jung YS AD - National Creative Research Initiatives Center for Nuclear Receptor Signals, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. FAU - Cho, Sung Jin AU - Cho SJ AD - New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea. AD - Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Kim, Jina AU - Kim J AD - New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea. FAU - Lee, In-Kyu AU - Lee IK AD - Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Republic of Korea. AD - Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Kim, Young-Hoon AU - Kim YH AD - Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. FAU - Lee, Chul-Ho AU - Lee CH AD - Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. FAU - Jeong, Won-Il AU - Jeong WI AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. FAU - Jo, Eun-Kyeong AU - Jo EK AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon, Republic of Korea. FAU - Choi, Hueng-Sik AU - Choi HS AUID- ORCID: 0000-0002-3163-1572 AD - National Creative Research Initiatives Center for Nuclear Receptor Signals, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201208 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Esrrg protein, mouse) RN - 0 (GSK5182) RN - 0 (Interferon Type I) RN - 0 (Receptors, Estrogen) RN - 0 (Transcription Factor AP-1) RN - 094ZI81Y45 (Tamoxifen) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.6.1.- (Ddx58 protein, mouse) RN - EC 3.6.1.- (Ifih1 protein, mouse) RN - EC 3.6.4.13 (DEAD Box Protein 58) RN - EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1) RN - O84C90HH2L (Poly I-C) SB - IM CIN - J Leukoc Biol. 2021 May;109(5):857-859. PMID: 33527528 MH - Animals MH - DEAD Box Protein 58/metabolism MH - *Gene Expression Regulation/drug effects MH - Interferon Type I/*genetics/metabolism MH - Interferon-Induced Helicase, IFIH1/metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Macrophages/drug effects/*metabolism MH - Male MH - Mice, Inbred C57BL MH - Poly I-C/*pharmacology MH - Promoter Regions, Genetic MH - Protein Binding/drug effects MH - Receptors, Estrogen/genetics/*metabolism MH - Signal Transduction/drug effects MH - Tamoxifen/analogs & derivatives/pharmacology MH - Transcription Factor AP-1/metabolism MH - Mice OTO - NOTNLM OT - estrogen-related receptor gamma OT - macrophage OT - type I IFN EDAT- 2021/02/23 06:00 MHDA- 2021/05/06 06:00 CRDT- 2021/02/22 06:13 PHST- 2020/10/19 00:00 [revised] PHST- 2020/01/02 00:00 [received] PHST- 2020/11/09 00:00 [accepted] PHST- 2021/02/23 06:00 [pubmed] PHST- 2021/05/06 06:00 [medline] PHST- 2021/02/22 06:13 [entrez] AID - 10.1002/JLB.2HI1219-762R [doi] PST - ppublish SO - J Leukoc Biol. 2021 May;109(5):865-875. doi: 10.1002/JLB.2HI1219-762R. Epub 2020 Dec 8.