Abstract
Experimental evidence documents that the MDAโ7/ILโ24 protein (an ILโ10 family cytokine) binds to ILโ20 and ILโ22 receptor complexes resulting in the activation of JAK/STAT signaling pathways. Recent published reports utilizing human blood derived primary lymphocytes have provided additional confirmatory evidence relating to the cytokine properties of this molecule. A notable attribute of mdaโ7/ILโ24 is its cancer cellโspecific apoptosis inducing capacity, which currently remains incompletely understood. Treatment with distinctive tyrosine kinase inhibitors (Genistein and AG18) or a JAKโselective inhibitor (AG490) did not prevent Ad.mdaโ7 induced apoptosis in diverse cell lines. In addition, there is no apparent correlation between patterns of expression of ILโ20R1, ILโ20R2, and ILโ22R mRNA and susceptibility to Ad__.mdaโ7__ in different cell lines. Furthermore, Ad.mdaโ7 is able to induce killing in STAT/JAK deficient cells. In contrast, treatment with the p38^MAPK^ selective inhibitor SB203580, partially inhibited apoptosis induced by Ad__.mdaโ7__ in different cell lines. These results demonstrate for the first time that signaling events leading to susceptibility to Ad__.mdaโ7__ induced apoptosis, might be tyrosine kinase independent and can thus be distinguished from its cytokine function related properties mediated by the ILโ20/ILโ22 receptor complexes that require JAK/STAT kinase activity. J. Cell. Physiol. 196: 334โ345, 2003. ยฉ 2003 WileyโLiss, Inc.