[IFN-alpha and IFN-lambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity]
>>Cancer Biol Ther. 2008 Jul;7(7):nihpa47781.
IFN-alpha and IFN-lambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity.
Maher SG, Sheikh F, Scarzello AJ, Romero-Weaver AL, Baker DP, Donnelly RP, Gamero AM.
Department of Surgery, Trinity College Dublin, Dublin, Ireland.
Interferon (IFN)-lambda, also known as IL-28A, IL-28B or IL-29, is a new type III IFN, which like type I IFN-(alpha/beta), activates common elements of the JAK/STAT signaling pathway and exhibits antiproliferative activity. Currently, IFN-alpha is used in the treatment of certain forms of cancer, but its antitumor effects are limited and associated with high toxicity. In this study, we determined whether IFN-lambda induced the same level of cell growth inhibition relative to IFN-alpha. To this effect HaCaT cells, which are typically growth inhibited by IFN-alpha, underwent apoptosis in response to IFN-lambda. Next, in contrast to IFN-alpha stimulation, IFN-lambda prolonged the duration of activated STAT1 and STAT2. Furthermore, the kinetics of IFN-stimulated genes was different as IFN-lambda induced a delayed but stronger induction of IFN-responsive genes. Components of the JAK/STAT pathway remained essential for the antiproliferative effects of IFN-alpha and IFN-lambda. IFN-lambda-induced persistence of STAT activation required de novo protein synthesis and was in part due to a delay in STAT2 inactivation. Thus our data demonstrate that the duration of IFN-lambda signaling is different from that of IFN-alpha, and that IFN-lambda could be a suitable cytokine to evaluate for cancer therapy.<<
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