These data suggest that the airway response induced by the S1P signal is mediated by S1P3. Consistent with these reports, in the present study, continuous injection of fingolimod-P significantly increased bronchoconstriction, but the same dose of ASP4058 did not. The exact mechanism responsible for the pulmonary adverse event observed in the clinical trial of fingolimod is unknown; however, the effect of fingolimod on the airway response might be involved to some extent. Therefore, our data suggest that ASP4058 treatment presents less risk for adverse pulmonary events than nonselective S1P receptor agonists such as fingolimod. In summary, we show here that ASP4058 is a selective agonist of S1P1 and S1P5, which effectively treats rodents with EAE. Further, ASP4058 exhibited a wide safety margin for bradycardia and bronchoconstriction. We therefore consider ASP4058 a potential new therapeutic option for the treatment of patients with MS, which is safer than nonselective S1P receptor agonists such as fingolimod. ASP4058 may also be useful in treating other autoimmune diseases given its ability to significantly reduce the population of peripheral lymphocytes. Chronic inflammation results from a homeostatic imbalance, a phenomenon that also characterizes tumor development. IBD are characterized by various degrees of inflammation of the intestine causing epithelial damage, among others. In general, the intestinal epithelium is able to repair itself by the restitution of the epithelial layer. In response to chronic ulceration, Ulcer Associated Cell Lineage glands expressing particular trefoil factor and mucin molecules are found that appear to promote mucosal repair and healing. Both forms of IBD, CD and UC, have an inherent risk of progression into cancer with a similar occurrence in patients with colonic CD to that with UC to develop colitis-associated cancer. Repeated tissue destruction and repair together with oxidative damage can trigger mutagenesis and may serve as cancer initiating events. In this process, a possible causative role for mutated p53 tumor-suppressor gene is more and more evident. Indeed, point mutations often resulting in a p53 gain of function, have been identified in neoplastic progression of UC and were shown to promote inflammation induced progression into intestinal cancer. Inflammatory responses are often associated with remodeling of the extracellular matrix as evidenced in wound healing and tissue repair. Profound alterations in ECM expression and ECM binding integrin Staurosporine PKC inhibitor adhesion receptors have been found in a number of inflamed tissues. The intestinal basement membrane represents a specialized ECM network that separates epithelial cells from the underlying connective tissue and is mainly composed of collagen IV, laminins, perlecan and nidogens.