| First Author | Li J | Year | 2018 |
| Journal | Free Radic Biol Med | Volume | 124 |
| Pages | 541-549 | PubMed ID | 30061089 |
| Mgi Jnum | J:318548 | Mgi Id | MGI:6860100 |
| Doi | 10.1016/j.freeradbiomed.2018.07.002 | Citation | Li J, et al. (2018) Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation. Free Radic Biol Med 124:541-549 |
| abstractText | Inflammatory bowel disease (IBD) is associated with intense oxidative stress, contributes to colonic damage and tumorigenesis. Mitogen-activated protein kinase phosphatase 1 (Mkp-1) is an essential negative regulator of the innate immune response. However, its role in colitis, and its association with the nuclear factor-erythroid 2 related factor 2 (Nrf2), a master regulator of cytoprotection program against oxidative stress, in inflammatory response, is elusive. In this study, we found that increased expression of Mkp-1, Nrf2, and heme oxygenase 1 (Ho-1) was correlated in colonic tissues in patients with ulcerative colitis and Crohn's disease, as well as wild-type mice with colitis induced by dextran sodium sulfate (DSS). Mkp-1(-/-) mice were more susceptible to DSS-induced colitis with more severe crypt injury and inflammation. Mechanistically, directly interacting with the DIDLID motif of Nrf2, Mkp-1 increased Nrf2 stability and positively regulated the constitutive and lipopolysaccharide (LPS)-inducible Nrf2/Ho-1 expression. Conversely, upon exposure to LPS, Nrf2 activated Mkp-1 transcription through the antioxidant response elements in the promoter of Mkp-1. Our results revealed a novel link between Mkp-1 and Nrf2 signaling pathways in protecting against colonic inflammation. Mkp-1 might be a therapeutic target for IBD. |
