Modulation of IL-13 signal in allergic asthma.

---

Presentation Time: 08:15 AM - 08:30 AM
Abstract ID: 4547 - B

Presenting Author:
Archana Shankar , Graduate Student at Cincinnati Children’s Hosp. Med. Ctr., University of Cincinnati College of Medicine

Abstract:

Allergic asthma, a chronic airway inflammatory disease affecting over 300 million people worldwide, is primarily driven by Th2 cytokines such as interleukin-13 (IL-13). Although IL-13 signals through a Jak1/Tyk2/STAT6-driven pathway, activation of other pathways has been reported (e.g., STAT3, SRC). To better understand the totality of signaling intermediates activated by IL-13, we employed an unbiased, phospho-proteomics approach. To this end A549 cells, a human airway epithelial cell line, were stimulated with IL-13 for 15 minutes, and peptides containing a phosphorylated Serine, or Threonine reside were identified by mass spectrometry.  >1,200 individual phospho-peptides were identified, and 108 residues were found to be differentially phosphorylated. Based on string DB results, SRC (a non-receptor tyrosine kinase) was identified as a potentially novel IL-13-induced signaling intermediate activated in response to IL-13. Kinetic assessment of SRC activation suggested that it is activated within seconds of IL-13 stimulation, and that its activation preceded activation of canonical signaling intermediates like STAT6. Functionally, SRC antagonists reduced expression of multiple IL-13-induced gene in IL-13-treated A549 cells. Collectively, these data suggest that SRC may represent a novel signaling intermediate activated in response to IL-13, and that SRC antagonism may have therapeutic benefit in the treatment of asthma.