Effect of Retinoic Acid in a Mouse Model of Allergic Rhinitis

PURPOSE: All-trans retinoic acid (ATRA) modulates immune responses by affecting T cells. Several studies have revealed that allergic inflammation of the lower airways is negatively associated with the vitamin A concentration. However, the role of ATRA in allergic inflammation of the upper airways is unclear. We investigated the effects of ATRA in an allergic rhinitis mouse model. METHODS: BALB/c mice except control groups (CON group) were sensitized with and challenged intra-nasally with Dermatophagoides farina (AR group). The ATRA groups were administered ATRA intraperitoneally. The steroid groups were administered steroid intranasally (ST group). Allergic symptoms and the average eosinophil number were counted. Cytokines and transcription factors were measured by Real-Time PCR and Western blotting. Der f-specific immunoglobulin E (IgE) was measured. Flow cytometry results of CD4+CD25+Foxp3+ T cells were analyzed. RESULTS: The symptom scores were lower in the ATRA group than in the AR group and higher than in the CON group. The levels of IgE were lower in the ATRA group than in the AR group and higher than in the CON and ST groups. The levels of Foxp3, TGF-beta, and IL-10 mRNA, as well as the percentage of CD4+CD25+Foxp3+ T cells, were higher in the ATRA group than in theAR group. In the ATRA group the levels of IFN-gamma mRNA were higher, and the levels of GATA-3 and IL-4 mRNA, and ROR-gammat were lower. In Western blotting analyses, the expression patterns of all factors, except Foxp3, showed similar to those of mRNA expression. CONCLUSIONS: ATRA has anti-allergic effects in an allergic rhinitis model, and its underlying mechanisms mainly include the induction of regulatory T cells and the inhibition of Th2 responses.

The Serine Protease Inhibitor, 4-(2-aminoethyl) Benzene Sulfonyl Fluoride Hydrochloride, Reduces Allergic Inflammation in a House Dust Mite Allergic Rhinitis Mouse Model

PURPOSE: Serine protease inhibitors are involved in immune development, anti-inflammatory mechanisms, and tissue repair. In the present study, the serine protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) was evaluated for its prophylactic and therapeutic applications in a mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 5 groups: contol (CON), Dermatophagoides farinae (Derf), AR mice treated with AEBSF before sensitization (S), AR mice treated with AEBSF after challenge (C), and steroid groups. Derf was used as an allergen. AEBSF was administered before S or after C. Allergic symptom scores, eosinophil counts, proteolytic activity, interferon-gamma, interleukin (IL)-10 levels and serum Derf-specific IgE levels were measured. T-bet, GATA-3, Foxp3, IL-13, and transforming growth factor (TGF)-beta mRNA levels were determined using real-time polymerase chain reaction. CD4+CD25+Foxp3+ T cells were assessed using flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, IL-13 mRNA levels, and tissue eosinophil counts decreased in both the S and C groups (P<0.05). Additionally, the percentage of CD4+CD25+Foxp3+ T cells, IL-10 levels, and Foxp3 mRNA levels increased in the S and C groups compared with those in the Derf group (P<0.05). AEBSF treatment decreased the proteolytic activity in the S and C groups (P<0.05). CONCLUSIONS: Prophylactic and therapeutic treatment with AEBSF significantly reduces allergic airway inflammation and can induce regulatory T cells in a murine model of AR.

Selenoprotein S Suppression Enhances the Late Stage Differentiation of Proerythrocytes Via SIRT1

Selenoprotein S (SelS) is widely expressed in diverse tissues where it localizes in the plasma membrane and endoplasmic reticulum. We studied the potential function of SelS in erythrocyte differentiation using K562 cells stably overexpressing SelS wild-type (WT) or one of two SelS point mutants, U188S or U188C. We found that in the K562 cells treated with 1 microM Ara-C, SelS gradually declined over five days of treatment. On day 4, intracellular ROS levels were higher in cells expressing SelS-WT than in those expressing a SelS mutant. Moreover, the cell cycle patterns in cells expressing SelS-WT or U188C were similar to the controls. The expression and activation of SIRT1 were also reduced during K562 differentiation. Cells expressing SelS-WT showed elevated SIRT1 expression and activation (phosphorylation), as well as higher levels of FoxO3a expression. SIRT1 activation was diminished slightly in cells expressing SelS-WT after treatment with the ROS scavenger NAC (12mM), but not in those expressing a SelS mutant. After four days of Ara-C treatment, SelS-WT-expressing cells showed elevated transcription of beta-globin, gamma-globin, epsilon-globin, GATA-1 and zfpm-1, whereas cells expressing a SelS mutant did not. These results suggest that the suppression of SelS acts as a trigger for proerythrocyte differentiation via the ROS-mediated downregulation of SIRT1.