IL-4 Signal Transduction

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DESCRIPTION (provided by applicant): Cytokines are important modulators of the immune response that underlies the inflammatory process in atopic forms of asthma. IL-4 and IL-13 are important cytokines for the regulation of these asthmatic immune responses. Work over the past ten years has identified many signaling molecules activated by these cytokines and outlined the basic mechanisms by which binding of these cytokines to their receptor leads to this activation. What remains unknown is how these signaling events are integrated by the cell into a biologic response. We have begun to address this question by using Affymetrix oligonucleotide arrays to define how different signaling pathways activated by these cytokines regulate gene transcription. This work has identified novel genes induced by IL-4. We propose to determine if the proteins encoded for by these genes are important for IL-4 function. In addition, we will extend our work with microarrays to determine how activation of different signaling molecules by IL-4 converges in a coordinated regulation of gene expression. Finally, recent data suggest that polymorphisms in the genes encoding some of these signaling molecules are associated with either asthma or atopy. We will determine if these allelic variants lead to alteration in IL-4 induced gene expression. Together, these results will provide investigators in asthma research important information regarding the function of these cytokines.