SARM regulates CCL5 production in macrophages by promoting the recruitment of transcription factors and RNA polymerase II to the Ccl5 promoter
Authors
Gurtler, ClaudiaCarty, Michael
Kearney, Jay
Schattgen, Stefan A.
Ding, Aihao
Fitzgerald, Katherine A.
Bowie, Andrew G.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2014-05-15Keywords
AnimalsArmadillo Domain Proteins
Chemokine CCL2
Chemokine CCL5
Chemokine CXCL10
Cytoskeletal Proteins
Gene Expression Regulation
Interferon Regulatory Factors
Interleukin-1beta
Macrophages, Peritoneal
Mice
Mice, Knockout
NF-kappa B
Promoter Regions, Genetic
RNA Polymerase II
Tumor Necrosis Factor-alpha
Cells
Immunity
Immunology and Infectious Disease
Immunology of Infectious Disease
Infectious Disease
Metadata
Show full item recordAbstract
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 alpha 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-1beta, 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-kappaB 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.Source
J Immunol. 2014 May 15;192(10):4821-32. doi: 10.4049/jimmunol.1302980. Epub 2014 Apr 7. Link to article on publisher's siteDOI
10.4049/jimmunol.1302980Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34955PubMed ID
24711619Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1302980