IL-4 is an essential cytokine in the immune response, regulating T cell differentiation, B cell immunoglobulin production, and the activation of macrophages. These activities give IL-4 a pivotal role in allergic disease. IL-4 acts through binding to the IL-4 receptor (IL-4R), composed of IL-4Ra and the common gamma chain, gc. The results of IL-4 signaling on target cells can be broadly characterized as growth or gene regulation, activities, which are predominantly controlled by two distinct domains of IL-4Ra. Many IL-4-induced gene expression events require the activation of STAT6, which is regulated by the IL-4Ra Gene Regulation Domain. Our work is focused on understanding how IL-4Ra activates STAT6 and the result of this activation on target cell signaling events. The first specific aim is to structurally characterize the IL-4Ra Gene Regulation Domain, through mapping of this domain's minimal STAT6 activation sequence, determining the mobility of this sequence, and ascertaining the essential nature of this sequence in IL-4-mediated gene expression. The second and third specific aims will determine the role of STAT6 in IL-4- mediated negative signaling of mast cells and macrophages using STAT6- deficient mice. These experiments will yield a greater understanding of the structure-function relationship if IL-4Ra and STAT6, and an understanding of these functions in cell signaling and allergic disease.
| Bailey, Daniel P; Kashyap, Mohit; Bouton, L Andrew et al. (2006) Interleukin-10 induces apoptosis in developing mast cells and macrophages. J Leukoc Biol 80:581-9 |
| Wright, Harry V; Bailey, Daniel; Kashyap, Mohit et al. (2006) IL-3-mediated TNF production is necessary for mast cell development. J Immunol 176:2114-21 |
| Harris, Amanda L; Ryan, John J; Farrell, Nicholas (2006) Biological consequences of trinuclear platinum complexes: comparison of [[trans-PtCl(NH3)2]2mu-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with its noncovalent congeners. Mol Pharmacol 69:666-72 |
| Barnstein, Brian O; Li, Geqiang; Wang, Zhengqi et al. (2006) Stat5 expression is required for IgE-mediated mast cell function. J Immunol 177:3421-6 |
| Norozian, Farnaz; Kashyap, Mohit; Ramirez, Carlos D et al. (2006) TGFbeta1 induces mast cell apoptosis. Exp Hematol 34:579-87 |
| Mann-Chandler, Meredith N; Kashyap, Mohit; Wright, Harry V et al. (2005) IFN-gamma induces apoptosis in developing mast cells. J Immunol 175:3000-5 |
| Kashyap, Mohit; Bailey, Daniel P; Gomez, Gregorio et al. (2005) TGF-beta1 inhibits late-stage mast cell maturation. Exp Hematol 33:1281-91 |
| Gomez, Gregorio; Ramirez, Carlos D; Rivera, Juan et al. (2005) TGF-beta 1 inhibits mast cell Fc epsilon RI expression. J Immunol 174:5987-93 |
| Gomez, Gregorio; Gonzalez-Espinosa, Claudia; Odom, Sandra et al. (2005) Impaired FcepsilonRI-dependent gene expression and defective eicosanoid and cytokine production as a consequence of Fyn deficiency in mast cells. J Immunol 175:7602-10 |
| Bouton, L Andrew; Ramirez, Carlos D; Bailey, Daniel P et al. (2004) Costimulation with interleukin-4 and interleukin-10 induces mast cell apoptosis and cell-cycle arrest: the role of p53 and the mitochondrion. Exp Hematol 32:1137-45 |
Showing the most recent 10 out of 20 publications
