Modulation of interleukin (IL)-13 binding and signaling by the gammac chain of the IL-2 receptor.
Interleukin (IL)-13 and IL-4 are cytokine products of TH2 cells which exert similar effects in a variety of cell types. We recently described IL-13R expression on human renal cell and colon carcinoma cells and demonstrated that gammac 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, gammac 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 gammac in IL-13 binding and signaling, we have transfected a renal cell carcinoma cell line with gammac 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 gammac 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.
Obiri
N I
NI
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. obiri@a1.cber.fda.gov
Murata
T
T
Debinski
W
W
Puri
R K
RK
D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D053613:Janus Kinase 1; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D018793:Interleukin-13; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1