| First Author | Wakabayashi H | Year | 2012 |
| Journal | Clin Immunol | Volume | 144 |
| Issue | 3 | Pages | 272-82 |
| PubMed ID | 22868447 | Mgi Jnum | J:187992 |
| Mgi Id | MGI:5438875 | Doi | 10.1016/j.clim.2012.07.002 |
| Citation | Wakabayashi H, et al. (2012) Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice. Clin Immunol 144(3):272-82 |
| abstractText | MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFNgamma, naive Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFNgamma and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells. |
