Secreted IL-1α promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice.

Published on Jul 1, 2015in European Journal of Immunology5.532
· DOI :10.1002/EJI.201445195
Dandan Lin13
Estimated H-index: 13
(Soochow University (Suzhou)),
Lei Lei10
Estimated H-index: 10
(Soochow University (Suzhou))
+ 9 AuthorsHaiyan Liu15
Estimated H-index: 15
(Soochow University (Suzhou))
Sources
Abstract
Interleukin-1α is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1α in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1α in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1α aggravates liver damage and membrane IL-1α slightly protects mice from liver injury. Further studies showed that secreted IL-1α 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-1α 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-1α 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-1α play different roles in acute liver injury. Secreted IL-1α 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-1α could be a critical regulator during acute liver inflammation.
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