PT - JOURNAL ARTICLE AU - Xiaomin Wang AU - Mirek Mychajlowycz AU - Christine Lau AU - Carlos Gutierrez AU - Jeremy Scott AU - Chung-Wai Chow TI - Syk mediates BEAS-2B cell migration and proliferation, and HRV-induced expression of VEGF and IL-8 AID - 10.1124/jpet.111.186429 DP - 2011 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - jpet.111.186429 4099 - http://jpet.aspetjournals.org/content/early/2011/10/26/jpet.111.186429.short 4100 - http://jpet.aspetjournals.org/content/early/2011/10/26/jpet.111.186429.full AB - Syk is an immunoregulatory tyrosine kinase that was originally identified in leukocytes. It is a key regulator of innate immunity as well as hematopoietic cell differentiation and proliferation. A role for Syk in regulating normal cellular functions in non-hematopoietic cells is increasingly recognized. We have previously shown robust Syk expression in airway epithelium where it regulates the early inflammatory response to human rhinovirus (HRV) infections, and HRV cell entry by clathrin-mediated endocytosis. To test the hypothesis that Syk plays a role in modulating airway epithelial cell proliferation, migration and production of VEGF and IL-8, we studied the BEAS-2B human bronchial epithelial cell line and primary human airway epithelia from normal and asthmatic donors using Syk-specific pharmacologic inhibitors and siRNA. Using an in vitro 'wounding' model, we demonstrated significant impairment of 'wound' closure following treatment with the Syk inhibitors, R406 and Bay61-3606, over-expression of the kinase-inactive SykK396R mutant, and Syk knock-down by siRNA. HRV infection also impaired wound healing, an effect that was partly Syk-dependent as wound healing was further impaired when HRV infection occurred in the presence of Syk inhibition. Further investigation of potential regulatory mechanisms revealed that inhibition of Syk suppressed HRV-induced vascular endothelial growth factor (VEGF) expression while promoting activation of caspase-3, a mediator of epithelial cell apoptosis. Together, these results indicate that Syk plays a role in promoting epithelial cell proliferation and migration, while mitigating the effects of apoptosis.