The Combination of IFN-α2 and IFN-α8 Exhibits Synergistic Antiproliferative Activity on Renal Cell Carcinoma (RCC) Cell Lines Through Increased Binding Affinity for IFNAR-2
| Autor: | Mutsuko Taniguchi, Toshio Ariyasu, Madoka Taniai, Harumi Ariyasu, Yasuo Tsutsumi, Miho Aga, Shigeto Yamamoto, Yohei Mukai, Tsunetaka Ohta, Chie Ushio, Shigeharu Fukuda, Tadao Tanimoto |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Journal of Interferon & Cytokine Research. 27:517-524 |
| ISSN: | 1557-7465 1079-9907 |
| Popis: | Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8. To analyze the interactions between IFN-alpha2 and IFN-alpha8, the receptor-binding kinetics of different combinations of IFN-alpha2 and IFN- alpha8 to the IFN-alpha receptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (K(a)) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-alpha8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-alpha2 but not the other combinations. These findings indicate that the binding manner of IFN-alpha8 for IFNAR-2 is different from that of IFN-alpha2, suggesting that binding of IFN-alpha8 rather than binding of IFN-alpha2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC. |
| Databáze: | OpenAIRE |
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