Modulation of interleukin (IL)-13 binding and signaling by the gamma(c) chain of the IL-2 receptor

Interleukin (IL)-13 and IL-4 are cytokine products of T(H)2 cells which exert similar effects in a variety of cell types. We recently described IL-ISR expression on human renal cell and colon carcinoma cells and demonstrated that gamma(c) is not a component of IL-13R, or IL-4R systems in these cells, In lymphoid cells such as B cells and monocytes, which respond to IL-13, gamma(c) is a component of IL-4R but does not appear to be a component of IL-13R, Furthermore, while significant IL-13 binding is observed on carcinoma cells, IL-13 barely binds these lymphoid cells and the binding characteristics are different, To better understand the role of gamma(c) in IL-13 binding and signaling, we have transfected a renal cell carcinoma cell line with gamma(c) and examined IL-13 and IL-4 binding and signaling, IL-13 binding as well as IL-13 and IL-4 signaling through the JAK-STAT signaling pathway were severely inhibited, This inhibition was paralleled by a loss of expression of one of the IL-13R chains and intercellular cell adhesion molecule-1. Thus, although gamma(c) has been shown to enhance IL-4 binding and function in some cell types, its influence on IL-13R function in tumor cells appear to be largely negative.