Given that the symptoms of CSU, such as hives and angioedema, are largely driven by the release of histamine and other inflammatory mediators from activated mast cells, the observed decrease in mast cell activation and mediator production following siRNA-mediated knockdown of CCL2, CH25H, and TNF genes in our HMC-1 model suggests a potential mechanism by which these genes may contribute to CSU pathogenesis. The gene discussed is CCL2; the disease is angioedema.