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The generation of mice lacking the expression of the IRF3 transcription factor ( Irf3−/− mice) has revealed its crucial role in the activation of the type I IFN response. The Bcl2l12 gene, encoding Bcl2L12 protein structurally related to the Bcl-2 family, was found to almost overlap with the Irf3 gene, and the null mutation previously introduced into the Irf3 allele resulted in the functional inactivation of the Bcl2l12 gene; therefore, the mice are correctly termed Irf3−/−Bcl2l12−/− mice. Embryonic fibroblasts from Irf3−/−Bcl2l12−/− mice ( Irf3−/−Bcl2l12−/− MEFs) showed resistance to DNA damage-induced apoptosis, accompanied by impaired caspase cleavage. This apoptotic defect in Irf3−/−Bcl2l12−/− MEFs was rescued by the ectopic expression of Bcl2L12, but not IRF3. The Bcl2L12-mediated apoptotic response depended on the cell type and extracellular stimulus. In contrast, the previously reported defect in the induction of type I IFN genes by nucleic acids in Irf3−/−Bcl2l12−/− MEFs was rescued by expressing IRF3, but not Bcl2L12. Thus, our present study revealed, on the one hand, a cell type-dependent proapoptotic function of Bcl2L12 and, on the other hand, confirmed the essential role of IRF3 in type I IFN response.

30 Mar 2007·Clinical and Experimental ImmunologyQ3 · MEDICINE

Allergenic epitopes of ovalbumin (OVA) in patients with hen’s egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide

Q3 · MEDICINE

Article

Author: Saito, K ; Kohno, Y ; Hosoya, T ; Suzuki, N ; Horiuchi, T ; Niimi, H ; Shimojo, N ; Tsunoo, H ; Honma, K ; Hayashi, H

SUMMARYWe studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347–385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. These results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVA-B1). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.

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Pipeline Snapshot as of 26 Apr 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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