Detection of Chemokine Gene Expression Induced by IL-12/IL-2 in Renca Tumor

Park, Jong Wook; Yoon, Soo Jung; Suh, Seong Il; Han, In Sook; Kim, Young Kwon

Abstract

In order to evaluate antitumor rnechanisms of interleukin (IL)-12/IL-2 that has been shown significant tumor suppressive activity on established primary and metastatic Renca tumor, we studied chemokine gene expression induced by direct action of IL- 12/IL-2 or cytokine cascade. IL-12/IL-2 induced gene expression of interferon gamma (IFN-r) and granulocyte monocyte-colony stimulating factor (GM-CSF) in splenocytes, and it induced gene expression of monokine induced by IFN-r (Mig), interferon inducible protein 10 (IP- 10), SDF-1, macrophage inflammatory protein (MIP)-1a, MIP-1B, MIP-2, monocyte chemotactic protein (MCP)-1, and Rantes in tumor mass. However IL-12/IL-2 could not induce these chemokines in tumor mass of GKO mice and Renca cell in vitro. IL- 12 also did not increased chemokine gene expression in Renca cell in vitro, but IFN-r induced gene expression of Mig, IP-10, MCP-1 in Renca cell in vitro. In the chemotaxis assay, culture supernatant of Renca cell stimulated with IFN-r increased splenocyte migration in vitro. All these data suggest IL-12/IL-2 can induce IFN-r-chemokine cascade in tumor mass, and Mig, IP-10, MCP-1 produced from tumor cell may play an important role for initial immune cell migration into tumor mass.