Expression of Sox11 and Brn transcription factors during development and following transient forebrain ischemia in the rat.

Sox11 is a transcription factor that is proposed to be involved in the development and regeneration of the brain [M.P. Jankowski, P.K. Cornuet, S. Mcllwrath, H.R. Koerber, K.M. Albers, SRY-box containing gene 11 (Sox11) transcription factor is required for neuron survive and neurite growth, Neuroscience 143 (2006) 501-514]. In this study, we compared the expression patterns of Sox11 and its two putative binding partners, Brn1 and Brn2 during development and following transient forebrain ischemia in the rat. The spatiotemporal expression pattern of Brn1 was similar to that of Sox11 from the late embryonic to postnatal development, and they are strongly expressed in the brain regions where neuronal progenitors and immature neurons are enriched. On the other hand, Brn2 was ubiquitously expressed in most tissues including developing nervous system. Neuronal depolarization of cerebral cortex neurons in vitro enhanced both Sox11 and Brn1 expression, whereas the induction of Brn2 was only marginal, further suggesting the similar transcriptional modulation of Sox11 and Brn1. In the hippocampus, however, they showed a little different expression patterns. The expression of Brn1 was not substantial in developing dentate gyrus (DG) where Sox11 expression was strong. The transient forebrain ischemia enhanced Sox11 gene expression moderately in the CA1 and strongly in the DG, whereas Brn1 was selectively induced only in the CA1 of the hippocampal formation. Collectively, overall results suggest that the expression of Sox11 and Brn1 may be modulated by the cell-type specific machinery.

Increased expression of endothelial cell adhesion molecules due to mediator release from human foreskin mast cells stimulated by autoantibodies in chronic urticaria sera.

Histamine-releasing antibodies that act against the epitope of the alpha chain of Fc(epsilon)RI (anti-Fc(epsilon)RI(alpha) antibody) that may affect pathogenesis in serum of patients with chronic urticaria. We assessed the capability of anti-Fc(epsilon)RI(alpha) antibody in sera from patients with chronic urticaria to release histamine and cytokines, and to induce the expression of endothelial cell adhesion molecules. We also assessed the release of inflammatory mediators from cultured foreskin mast cells, and expression of endothelial cell adhesion molecules on human dermal microvascular endothelial cells. Cells were pretreated with mast cell-conditioned media: culture media of mast cells treated with sera from chronic urticaria patients containing anti-Fc(epsilon)RI(alpha) antibody. Histamine release from human foreskin mast cells challenged with sera, increased after both 20 min and 16 h intervals. Leukotriene D4 release also increased at both 20 min and 16 h. Tumor necrosis factor-alpha increased significantly in foreskin mast cell culture challenged with sera of chronic urticaria patients. After the stimulation of human dermal microvascular endothelial cells with the conditioned media, the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin increased significantly. Treatment of the conditioned media with anti-tumor necrosis factor-alpha monoclonal antibody partially inhibited the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The data suggest that sera from patients with chronic urticaria containing anti-Fc(epsilon)RI(alpha) antibody release mediators and tumor necrosis factor-alpha by activating human foreskin mast cells. This release can play a pathogenic role in chronic urticaria by activating endothelial cells, in part due to the actions of tumor necrosis factor-alpha from mast cells.