| First Author | Sakai J | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 1428 |
| PubMed ID | 28469251 | Mgi Jnum | J:275077 |
| Mgi Id | MGI:6296083 | Doi | 10.1038/s41598-017-01600-y |
| Citation | Sakai J, et al. (2017) Lipopolysaccharide-induced NF-kappaB nuclear translocation is primarily dependent on MyD88, but TNFalpha expression requires TRIF and MyD88. Sci Rep 7(1):1428 |
| abstractText | TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-kappaB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-kappaB translocation. We tested the model proposed by Cheng et al. using real-time single cell analysis in macrophages expressing EGFP-tagged p65 and a TNFalpha promoter-driven mCherry. Following LPS stimulation, cells lacking TRIF show a pattern of NF-kappaB dynamics that is unaltered from wild-type cells, but activation of the TNFalpha promoter is impaired. In macrophages lacking MyD88, there is minimal NF-kappaB translocation to the nucleus in response to LPS stimulation, and there is no activation of the TNFalpha promoter. These findings confirm that signalling through MyD88 is the primary driver for LPS-dependent NF-kappaB translocation to the nucleus. The pattern of NF-kappaB dynamics in TRIF-deficient cells does not, however, directly reflect the kinetics of TNFalpha promoter activation, supporting the concept that TRIF-dependent signalling plays an important role in the transcription of this cytokine. |
