Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is an inducible terminal enzyme in the synthetic pathway for PGE₂, which has been demonstrated to participate in many peripheral pathological inflammatory processes. Recently, we demonstrated that mPGES-1 also has a role in brain inflammation, such as that following cerebral ischemia. The expressions of mPGES-1 and cyclooxygenase-2 (COX-2) were induced and co-localized in neurons, microglia and endothelial cells in the cerebral cortex after transient focal ischemia. Using mPGES-1 knockout (KO) mice in which the postischemic PGE₂ production in the cortex was completely absent, we found that the ischemic injuries were reduced compared to those in wild-type (WT) mice. Furthermore, the ameliorated symptoms observed in KO mice after ischemia were reversed to almost the same severity as in WT mice by intracerebroventricular injection of PGE₂ into KO mice, suggesting the involvement of mPGES-1 in the exaggeration of ischemic injury through PGE₂ production. The induction and involvement of mPGES-1 in neurotoxicity were also observed in a glutamate-induced excitotoxicity model using rodent hippocampal slices. Glutamate increased the expression of mPGES-1 and production of PGE₂. The protective effect of NS-398, an inhibitor of COX-2, on the excitotoxicity observed in WT slices was completely abolished in mPGES-1 KO slices, which showed less excitotoxicity than WT slices. In the transient focal ischemia model, injection of NS-398 reduced not only ischemic PGE₂ production, but also ischemic injuries in WT mice, but not in mPGES-1 KO mice, which showed less dysfunction than WT mice. Our observations suggest that mPGES-1 is a critical determinant of postischemic neurological dysfunctions and that mPGES-1 and COX-2 are co-induced and co-localized by excess glutamate and act together to exacerbate stroke injury through excessive PGE₂ production. Considering that COX-2 inhibitors may non-selectively suppress the production of many types of prostanoids that are essential for normal physiological function of the brain and that a large number of epidemiological studies have provided evidence of an increased cardiovascular risk associated with the use of COX-2, an mPGES-1 inhibitor may prove to be an injury-selective inhibitor with fewer side effects. Thus, the results from mPGES-1 KO mice suggest that mPGES-1 is a promising novel target for the treatment of human stroke.

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Some patients with malignant or stenotic inflammatory lesions of the trachea require tracheal resection and reconstruction. Conventionally, it is difficult to reconstruct tracheal defects by either end-to-end anastomosis or autologous tissue implantation.
Recently, a few studies on tracheal regeneration using scaffolds have been reported. Collagen-conjugated prothesis have been used for tracheal reconstruction in the clinical application. The problem of this tracheal prosthesis is delay of epithelial regeneration to avoid possible infection.
A bio-engineered scaffold consisted of collagen sponge and polypropylene mesh with fibroblasts was developed for accelerating tracheal regeneration.
The regenerated tracheas were examined by bronchoscopic findings, histological finding and measurement of average thickness of the regenerated trachea. A bio-engineered scaffold was observed to induce more rapid re-epithelization in the large tracheal defect of a rabbit model. This method appears to be feasible for clinical use after further experiments investigating its efficacy and safety.

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Immunoglobulin A (IgA) is the body's predominant antibody isotype, and the bulk of the body's IgA-producing cells reside in various mucosal and exocrine tissues. Production of IgA at mucosal surfaces is strictly regulated through coordinated communication among mucosal B and T cells, mucosal dendritic cells (DCs), and epithelial cells. Although organized lymphoid tissues such as Peyer's patches (PP) have long been recognized as key sources of IgA plasma cells at mucosal surfaces, IgA-mediated mucosal immune response is maintained even in PP-null conditions. Mucosal DCs likely are specialized to provide help to B cells to promote IgA-producing plasma cells. Intriguingly, induction of the proliferation of microbiota-specific IgA⁺ B cells is independent of T helper activity but may depend on lamina propria DCs expressing iNOS, CX3CR1, and TLR5.
In the quest to develop an oral vaccine to boost mucosal immunity, rice was genetically engineered to express the B subunit of cholera toxin (CT-B). The recombinant CT-B that accumulates in the protein bodies of rice is resistant to the harsh gastrointestinal environment, and immunization of mice with the vaccine provoked a protective mucosal IgA response against CT. Furthermore, the vaccine is stable and maintains immunogenicity at room temperature for at least 24 months. Because they are easy to administer and requires neither refrigeration nor needles, rice-based mucosal vaccines are highly practical for global immunization against infectious diseases.

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ADP ribosylation factors (ARFs), a family of small GTPases, play an important role in membrane trafficking and actin cytoskeletal rearrangement. For the activation of ARFs, the exchange of GDP for GTP that is catalyzed by guanine nucleotide exchange factors (GEFs) is necessary. We previously identified a novel guanine nucleotide exchange protein (GEP) for ARF with a molecular size of ∼100-kDa (ARF-GEP100, GEP100), which preferentially activates ARF6. Our current work has focused on investigating the role of GEP100 in leukocytes. In the present study we report findings suggesting that GEP100 is involved in the Fc and complement receptor-mediated phagocytosis in human macrophage-like differentiated human U937 cells, through RNAi knockdown experiments on GEP100.
Here, we briefly review ARFs and ARF-GEFs, and introduce a novel GEP100 function, namely the involvement of phagocytosis in monocyte/macrophage-like cells.

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It is well established that All-trans retinoic acid (RA) regulates the growth and differentiation of a wide variety of tissues and cell types. Here we found that RA has a new role, the breast cancer resistance protein (Abcg2) inhibitor. RA, like the transporter inhibiter reserpine, dose-dependently reduced the efflux of Hoechst dye from HSCs by inhibiting the Abcg2 transporter without requiring new transcription. The effects of RA and reserpine on the SP were reversible upon wash-out. Similar results were obtained in NIH3T3-GFP cells stably expressing Abcg2. RA-treated and Abcg2-deficient HSCs showed increased sensitivity to doxorubicin, a type of anthracycline. Our evidence suggests that, besides playing crucial roles in the survival, growth, and differentiation of HSCs, RA has a novel function as an inhibitor of the Abcg2 transporter.

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Human apotransferrin was examined for its sensitivity to myeloperoxidase (MPO), a haem enzyme and an oxidant in neutrophils. Exposure of apotransferrin to a system composed of MPO, hydrogen peroxide and chloride at moderately acidic pH, but not at neutral to alkaline pH, altered its ultraviolet absorption spectrum. This reaction was not observed when MPO, hydrogen peroxide or chloride was omitted, when MPO was replaced by heated MPO, or when an inhibitor of haem enzymes, cyanide or azide, was added to the reaction system. These findings suggest that the degradation of apotransferrin by the MPO-hydrogen peroxide-chloride system was due to oxidation and damage of the protein moiety of apotransferrin.

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