| First Author | Wang S | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4246 |
| PubMed ID | 30315268 | Mgi Jnum | J:267593 |
| Mgi Id | MGI:6267747 | Doi | 10.1038/s41467-018-06568-5 |
| Citation | Wang S, et al. (2018) REV-ERBalpha integrates colon clock with experimental colitis through regulation of NF-kappaB/NLRP3 axis. Nat Commun 9(1):4246 |
| abstractText | The roles of Rev-erbalpha and circadian clock in colonic inflammation remain unclarified. Here we show colon clock genes (including Rev-erbalpha) are dysregulated in mice with DSS-induced colitis. In turn, disruption of the circadian clock exacerbates experimental colitis. Rev-erbalpha-deficient mice are more sensitive to DSS-induced colitis, supporting a critical role of Rev-erbalpha in disease development. Further, Rev-erbalpha ablation causes activation of Nlrp3 inflammasome in mice. Cell-based experiments reveal Rev-erbalpha inactivates Nlrp3 inflammasome mainly at the priming stage. Rev-erbalpha directly represses Nlrp3 transcription through specific binding to the promoter region. Additionally, Rev-erbalpha represses p65 transcription and indirectly repressed Nlrp3 via the NF-kappaB pathway. Interestingly, Rev-erbalpha activation in wild-type mice by SR9009 attenuates DSS-induced colitis, whereas the protective effects are lost in Nlrp3(-/-) and Rev-erbalpha(-/-) mice. Taken together, Rev-erbalpha regulates experimental colitis through its repressive action on the NF-kappaB/Nlrp3 axis. Targeting Rev-erbalpha may represent a promising approach for prevention and management of colitis. |
