House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation. (1/54)

In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.  (+info)

Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice. (2/54)

In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-alpha, IL-1beta, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-alpha in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.  (+info)

Endotoxin and house dust mite allergen levels on synthetic and buckwheat pillows. (3/54)

Pillows are known to contain significant levels of indoor allergens and endotoxin, that are of importance to house dust mite sensitized asthmatics. Buckwheat pillows are commonly used in Korea. We studied the levels of the house dust mite allergen, Der f 1, and endotoxin on new synthetic and buckwheat pillows and their accumulation over three months. Endotoxin levels were significantly higher on new buckwheat pillows compared to synthetic pillows; geometric mean levels (95% CI) were 60,950 EU/g (30,270-122,700) and 4,887 EU/g (2,570-9,311) respectively (p<0.001). No Der f 1 was detected on the new pillows. After three months Der f 1 levels were similar on buckwheat and synthetic pillows, geometric mean levels (95% CI) were 1.16 microg/g (0.02-8.13) and 1.08 microg/g (0.19-1.68) respectively. These results indicate that buckwheat pillows are a source of very high endotoxin levels that may be of relevance to asthma severity of atopic asthmatics.  (+info)

Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides farinae specific allergic individuals: involvement of protein kinase C-alpha. (4/54)

The major house-dust mite allergen, Der f 2, stimulates the phospholipase D (PLD) in T lymphocytes from Dermatophagoides farinae specific allergic individuals. PLD activity increased more than two-fold in T cells from allergic patients compared with those cells from normal controls with maximal responses within 30 min after exposure of Der f 2. A well-known PLD activator PKC-alpha was found to be translocated to membrane from cytosol in Der f 2-treated T cells from Dermatophagoides farinae specific allergic individuals. Down-regulation of PKC-alpha with phorbol myristate acetate pretreatment for 24 h abolished Der f 2-induced PLD activation. Ro 320432, PKC inhibitor also reduced the effects of Der f 2-induced PLD activation suggesting that PKC-alpha acts as upstream activator of PLD in Der f 2-treated T cells. Taken together, the present data suggest that Der f 2 can stimulate PLD activity through the PKC-alpha activation in T cells from Dermatophagoides farinae allergic individuals.  (+info)

Somatropin promotes dermatophagoides farinae-specific IgE generation independently of IL-4 and IL-10. (5/54)

Interleukin (IL)-10 accelerates the IgE production of anti-CD40- and IL-4-stimulated PBMC by enhancing the IL-6 production of T lymphocytes or antigen-primed spleen cells, in addition to its role as a regulator of the inflammatory responses. To further investigate the mechanisms enhancing IgE synthesis, we determined the effect of somatropin as well as IL-10 on the secretion of Dermatophagoides farinae (Df)-specific IgE by K7 cells, which originate from an EBV-immortalized cell line. Df-pulsed autologous T cells, as well as the supernatants of these cultures, increased the synthesis of Df-specific IgE. Antigen-specific IgE was also enhanced when K7 cells were treated with anti-CD40 antibody and with both IL-4 and IL-10, or with IL-4 and IL-10 without anti-CD40 antibody. The treatment of K7 cells with anti-CD40 antibody and IL-4, or anti-CD40 antibody and IL-10 did not increase IgE production. The Df-specific IgE activity of the supernatants of K7 cells treated with somatropin alone was increased significantly although somatropin did not show any additive effect on the IgE production of anti-CD40 antibody-treated cells. The results indicate that IL-10, a Th2-type cytokine, directly affects the mature B cells that produce IgE, and that the secretion of IgE is increased by treatment with IL-10 in cells that are stimulated with anti-CD40 and IL-4 at the level of the EBV-immortalized cell line, which has already switched to IgE production. Somatropin similarly stimulates activated mature B cells to enhance their production of antigen-specific IgE without class switching, independently of IL-4 and IL-10.  (+info)

Multiple-mutation at a potential ligand-binding region decreased allergenicity of a mite allergen Der f 2 without disrupting global structure. (6/54)

We assessed the effect of multiple-mutations within one IgE-binding area on allergenicity of Der f 2. The triple-mutant of Der f 2, P34/95/99A, exhibited the most significant reduction of allergenicity and circular dichroism analysis showed that the global structure of Der f 2 was maintained in P34/95/99A. These results indicate that such a strategy is effective when designing allergen-vaccines, which achieve less allergenicity for a broad population of patients without disrupting the global structure. Structurally, Der f 2 is a member of the MD-2 related lipid-recognition proteins. The sites for the triple-mutation located on the characteristically charged entrance of a cavity and corresponded to the regions critical to ligand-binding in the Niemann-Pick type 2 disease protein and MD-2.  (+info)

Expression of a major house dust mite allergen gene from Dermatophagoides farinae in Lotus japonicus accession Miyakojima MG-20. (7/54)

Transformation of a model legume Lotus japonicus accession Miyakojima MG-20 was examined using Agrobacterium tumefaciens with a binary expression vector. Using the improved transformation method, we introduced a major allergen gene from a house dust mite, Der f 1, into MG-20. Analyses by Southern hybridization, reverse transcription (RT)-PCR, and Western blotting showed that the Der f 1 gene was integrated into the genome of L. japonicus, expressing the gene product in the T1 lines. Our results imply future application of oral allergen-specific immunotherapy using legume plants.  (+info)

Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: a multi-center, double-blind, randomized, and placebo-controlled study in Taiwan. (8/54)

Sublingual immunotherapy (SLIT) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies, though more data is needed from well-controlled studies for documenting its efficacy in different ethnic populations. Ninety-seven children (age range 6-12 years), mild-to-moderate asthma with a single sensitization to mite allergen, were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with standardized mite extracts, which contain Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.). Patients were double blinded and randomly assigned to either a SLIT or placebo group. Following 24 weeks of study period, symptom and medication scores, lung function tests, skin prick tests, total serum IgE, and specific IgE to D.p. and D.f. were recorded. The results showed that there was statistically significant difference between these two groups in the analysis of daily (P=0.011), nighttime (P=0.028), and daytime (P=0.009) asthmatic scores after 24 weeks of treatment. Patients receiving SLIT improved their forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory flow (PEF) as compared to baseline (P=0.042, P=0.048, and P=0.001, respectively). No differences were found in skin prick test, total serum IgE and specific IgE to D.p. and D.f. Tolerance with high-dose SLIT was good with few minor adverse events reported. Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan.  (+info)