| First Author | Lin D | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 7 | Pages | 2084-98 |
| PubMed ID | 25870999 | Mgi Jnum | J:229694 |
| Mgi Id | MGI:5753010 | Doi | 10.1002/eji.201445195 |
| Citation | Lin D, et al. (2015) Secreted IL-1alpha promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice. Eur J Immunol 45(7):2084-98 |
| abstractText | Interleukin-1alpha is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1alpha in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1alpha in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1alpha aggravates liver damage and membrane IL-1alpha slightly protects mice from liver injury. Further studies showed that secreted IL-1alpha promotes T-cell activation. It also increased the expansion of CD11b(+) Gr1(+) myeloid cells, which may serve as a negative regulator of acute liver inflammation. Moreover, secreted IL-1alpha induced IL-6 production from hepatocytes. IL-6 neutralization reduced the proliferation of CD11b(+) Gr1(+) myeloid cells in vivo. CCL2 and CXCL5 expression was increased by secreted IL-1alpha in vitro and in vivo. Antagonists of the chemokine receptors for CCL2 and CXCL5 significantly reduced the migration of CD11b(+) Gr1(+) myeloid cells. These results demonstrate that secreted and membrane IL-1alpha play different roles in acute liver injury. Secreted IL-1alpha could promote T-cell activation and the recruitment and expansion of CD11b(+) Gr1(+) myeloid cells through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1alpha could be a critical regulator during acute liver inflammation. |
