First Author | Sgadari C | Year | 1996 |
Journal | Blood | Volume | 87 |
Issue | 9 | Pages | 3877-82 |
PubMed ID | 8611715 | Mgi Jnum | J:32860 |
Mgi Id | MGI:80344 | Doi | 10.1182/blood.v87.9.3877.bloodjournal8793877 |
Citation | Sgadari C, et al. (1996) Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood 87(9):3877-82 |
abstractText | Interleukin 12 (IL-12), a multifunctional cytokine produced by macrophages and B-cell lines, induces interferon-gamma (IFN-gamma) production, stimulates growth of both T and natural killer cells, promotes Th1-type helper T-cell responses, and inhibits neovascularization. Because the human interferon-inducible protein 10 (IP-10) can also inhibit neovascularization, we tested whether IP-10, induced by IL-12 through the intermediate IFN-gamma, might be a mediator of IL-12 angiogenesis inhibition. We report here that murine IL-12 profoundly inhibited basic fibroblast growth factor (bFGF)-induced Matrigel neovascularization in vivo, and that this effect of IL-12 was neutralized by systemic administration of antibodies to either murine IFN-gamma or IP-10. Murine IL-12 induced murine IP-10 expression in mouse splenocytes, and human IFN-gamma induced human IP-10 expression in purified human endothelial cells, suggesting that IL-12 can induce IP-10 expression in certain cells. These results document the important role of IP-10 as a mediator of angiogenesis inhibition by IL-12, and raise the possibility that IP-10 may also contribute to the antitumor effect of IL-12. |