Involvement of integrin-linked kinase in capillary/tube-like network formation of human vascular endothelial cells

Angiogenesis is a complex process involving an ECM and vascular endothelial cells (EC), and is regulated by various angiogenic factors including VEGF. The ability to form a capillary/tube-like network is a specialized function of EC. Therefore, in vitro angiogenesis was assessed by a capillary/tube-like network formation assay. There are three angiogenic parameters: capillary length, number of capillaries, and relative capillary area per field. We evaluated capillary length per field in the assay. VEGF promoted capillary/tube-like network formation of EC in a type I collagen gel matrix in vitro. Moreover, we demonstrated the involvement of ILK in a VEGF signaling pathway mediating capillary/tube-like network formation of EC using dominant-negative, kinase deficient ILK. This is a straightforward assay to monitor responses of human vascular endothelial cells

IL-4 and IL-12 Polymorphisms are Associated with Response to Suplatast Tosilate, a Th2 Cytokine Inhibitor, in Patients with Atopic Dermatitis

Th2-related immune and inflammatory responses have been implicated in the pathogenesis of atopic dermatitis (AD), but few clinical lines of evidence have been reported regarding how and whether Th2-related responses are associated with other risk factors in the treatment of AD patients. In this study, the associations between the polymorphisms of genes related to the pathophysiology of AD and the efficacy of suplatast tosilate, an oral immunemodulator known to downregulate Th2-related allergic responses, were analyzed in adult patients with chronic AD. Patients were recruited from our previous study, where suplatast tosilate was evaluated for its efficacy when used in combination with topical steroids. The genotypes of 35 single nucleotide polymorphisms (SNPs) of 27 genes related to AD pathogenesis were then determined in 17 responders and 18 non-responders, as defined by the improvement rate in their AD skin scores. While no significant difference in the patient background was observed between responders and non-responders, significant associations were noted between the response to treatment with suplatast tosilate and three SNPs of IL-4 (-590C/T: P=0.04, -33C/T: P=0.04) and IL-12B (1188A/C: P=0.03), but not for the other SNPs. Of note, ethnic differences in the genotype frequencies of IL-4 -590C/T and IL-12B 1188A/C SNPs were found. In conclusion, the present results raise the possibility that AD patients who tend to produce more IL-4 and IL-12 may be susceptible to suplatast tosilate treatment and that ethnic variations should be considered to further understand the role of Th2-related responses