SARM Regulates CCL5 Production in Macrophages by Promoting the Recruitment of Transcription Factors and RNA Polymerase II to the Ccl5 Promoter
| العنوان: | SARM Regulates CCL5 Production in Macrophages by Promoting the Recruitment of Transcription Factors and RNA Polymerase II to the Ccl5 Promoter |
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| المؤلفون: | Jay Kearney, Andrew G. Bowie, Stefan A. Schattgen, Michael Carty, Katherine A. Fitzgerald, Claudia Gürtler, Aihao Ding |
| المصدر: | The Journal of Immunology. 192:4821-4832 |
| بيانات النشر: | The American Association of Immunologists, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | medicine.medical_treatment, Interleukin-1beta, Immunology, RNA polymerase II, Article, Mice, parasitic diseases, medicine, Animals, Immunology and Allergy, Promoter Regions, Genetic, Chemokine CCL5, Transcription factor, Chemokine CCL2, Armadillo Domain Proteins, Mice, Knockout, Messenger RNA, biology, Tumor Necrosis Factor-alpha, NF-kappa B, Signal transducing adaptor protein, RNA, Cell biology, Chemokine CXCL10, Cytoskeletal Proteins, Cytokine, Gene Expression Regulation, TRIF, Interferon Regulatory Factors, Macrophages, Peritoneal, biology.protein, Cancer research, Tumor necrosis factor alpha, RNA Polymerase II |
| الوصف: | The four Toll/IL-1R domain–containing adaptor proteins MyD88, MAL, TRIF, and TRAM are well established as essential mediators of TLR signaling and gene induction following microbial detection. In contrast, the function of the fifth, most evolutionarily conserved Toll/IL-1R adaptor, sterile α and HEAT/Armadillo motif-containing protein (SARM), has remained more elusive. Recent studies of Sarm−/− mice have highlighted a role for SARM in stress-induced neuronal cell death and immune responses in the CNS. However, whether SARM has a role in immune responses in peripheral myeloid immune cells is less clear. Thus, we characterized TLR-induced cytokine responses in SARM-deficient murine macrophages and discovered a requirement for SARM in CCL5 production, whereas gene induction of TNF, IL-1β, CCL2, and CXCL10 were SARM-independent. SARM was not required for TLR-induced activation of MAPKs or of transcription factors implicated in CCL5 induction, namely NF-κB and IFN regulatory factors, nor for Ccl5 mRNA stability or splicing. However, SARM was critical for the recruitment of transcription factors and of RNA polymerase II to the Ccl5 promoter. Strikingly, the requirement of SARM for CCL5 induction was not restricted to TLR pathways, as it was also apparent in cytosolic RNA and DNA responses. Thus, this study identifies a new role for SARM in CCL5 expression in macrophages. |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1302980 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a25e37d8d8c9ee70398debe1d2c939ba https://doi.org/10.4049/jimmunol.1302980 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a25e37d8d8c9ee70398debe1d2c939ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.1302980 |