Dietary supplementation with fructooligosaccharides attenuates airway inflammation related to house dust mite allergen in mice.

Fructooligosaccharides (FOS) are prebiotic supplements that can enhance immunological responses in the host to activate mucosal immunity, probably through regulation of gastrointestinal microflora. An area that has not been investigated, however, is the therapeutic potential of prebiotics on allergic airway diseases. The purpose of this study is to evaluate the effects of dietary supplementation with FOS on a murine model of allergic airway inflammation induced by the house dust mite allergen Dermatophagoides farinae (Der f). Male C3H/HeN mice were intratracheally administered with Der f and were fed a diet containing 0% or 2.5% FOS ad libitum. Supplementation with FOS alleviated mite allergen-related airway inflammation characterized by eosinophilic inflammation and goblet cell hyperplasia, which was evidenced by cytological and histological examinations. In addition, the FOS-supplemented diet reduced the serum allergen-specific IgG1 level as compared with a control diet in the presence of the mite allergen. Moreover, FOS tended to suppress the expression of IL-5 and eotaxin in the lungs, which is enhanced by mite allergen. These results suggest that dietary supplementation with FOS can prevent/improve allergic airway inflammation induced by the mite allergen. This effect can be at least partially associated with the inhibition of allergen-specific Ig production and probably with that of IL-5 and eotaxin expression.

Size effects of polystyrene nanoparticles on atopic dermatitislike skin lesions in NC/NGA mice.

Nano-sized particles are diffusing in the environment with the development of nanotechnology. Polystyrene (PS) nanoparticles are modified industrial products and pharmaceutical agents, however, adverse effects of PS nanoparticles remain to be elucidated. In the present study, we investigated the effects of PS nanoparticles with different sizes on the atopic dermatitis (AD)-like skin lesions in NC/Nga mice assumed to show the skin barrier defect/dysfunction in the presence or absence of mite allergen. Male NC/Nga mice were injected intradermally with three different-sized PS nanoparticles (25, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the local protein expression of inflammatory molecules in the ear and Ig production in serum. PS nanoparticles aggravated AD-like skin lesions related to mite allergen, which was paralleled by the local protein levels of interleukin-4, CCL2/monocyte chemotactic protein-1, CCL3/macrophage inflammatory protein-1 alpha, and CCL4/macrophage inflammatory protein-1 beta. In contrast, PS nanoparticles decreased interferon-gamma expression. Furthermore, exposure to PS nanoparticles induced ear swelling and CC-chemokine expression in the absence of allergen. These effects were greater with the smaller PS nanoparticles than with the larger ones regarding overall trend. These results suggest that exposure to PS nanoparticles under skin barrier defect/dysfunction can exacerbate AD-like skin lesions related to mite allergen in a size-dependent manner. The enhancing effects may be accounted for by T helper 2-biased immune responses. Furthermore, PS nanoparticles can evoke skin inflammation via the overexpression of CC-chemokines even in the absence of allergen in atopic subjects.

Runx3 expression in gastrointestinal tract epithelium: resolving the controversy.

We reported earlier that RUNX3 is expressed in human and mouse gastrointestinal tract (GIT) epithelium and that it functions as a tumor suppressor in gastric and colorectal tissues. However, there have been conflicting reports describing the absence of Runx3 in GIT epithelial cells. A part of the controversy may be derived from the use of a specific antibody by other groups (referred to as G-poly). Here, we show further evidence to support our earlier observations and provide a possible explanation for this apparent controversy. We generated multiple anti-RUNX3 monoclonal antibodies and found that RUNX3 antibodies recognizing the RUNX3 N-terminal region (residues 1-234) react with RUNX3 in gastric epithelial cells, whereas those recognizing the C-terminal region (beyond residue 234) did not. G-poly primarily recognizes the region beyond 234 and hence, is unable to detect Runx3 in this tissue.

Pulmonary exposure to carbon black nanoparticles increases the number of antigen-presenting cells in murine lung.

Particulate matters can enhance antigen-related airway inflammation and immunoglobulin production. The present study was designed to determine the effects of different sizes of nanoparticles on the antigen-presenting cells (APC) in the lung. ICR mice were exposed to vehicle, carbon black (CB) nanoparticles (14 nm or 56 nm), ovalbumin (OVA), or OVA + nanoparticles intratracheally. The expression of major histocompatibility complex (MHC) class II, costimulatory molecules (CD80, CD86, CD11c), and DEC205 (dendritic cell marker), F4/80 (macrophage marker), and CD19 (B-cell marker) in the lung cells was measured by flow cytometry. 14 nm nanoparticles, but not 56 nm nanoparticles, increased the number of the total lung cells. Combination of OVA and 14 nm or 56 nm nanoparticles increased the total lung cells. The expression of MHC class II and/or costimulatory molecules and the number of APC in the lung were increased by 14 nm nanoparticles in the presence or absence of OVA. The increases were more prominent with combination of OVA and 14 nm nanoparticles. 56 nm nanoparticles did not show any significant effects. 14 nm CB nanoparticles can increase the expression of MHC class II and costimulatory molecules and the number of APC in the lung, especially in the presence of antigen, which can result in subsequent antigen-related airway inflammation and immunoglobulin production.

Components of diesel exhaust particles differentially affect Th1/Th2 response in a murine model of allergic airway inflammation.

BACKGROUND: Diesel exhaust particles (DEP) can enhance various respiratory diseases. However, it is unclear as to which components in DEP are associated with the enhancement. We investigated the effects of DEP components on antigen-related airway inflammation, using residual carbonaceous nuclei of DEP after extraction (washed DEP), extracted organic chemicals (OC) in DEP (DEP-OC), and DEP-OC plus washed DEP (whole DEP) in the presence or absence of ovalbumin (OVA). METHODS: Male ICR mice were intratracheally administrated with OVA and/or DEP components. We examined the cellular profile of bronchoalveolar lavage (BAL) fluid, histological changes, lung expression of inflammatory molecules, and antigen-specific production of IgG1 in the serum. RESULTS: DEP-OC, rather than washed DEP, enhanced infiltration of inflammatory cells into BAL fluid, magnitude of airway inflammation, and proliferation of goblet cells in the airway epithelium in the presence of OVA, which was paralleled by the enhanced lung expression of eotaxin and IL-5 as well as the elevated concentration of OVA-specific IgG1. In contrast, washed DEP with OVA showed less change and increased the lung expression of IFN-gamma. The combination of whole DEP and OVA caused the most remarkable changes in the entire enhancement, which was also accompanied by the enhanced expression of IL-13 and macrophage inflammatory protein-1 alpha. CONCLUSION: DEP-OC, rather than washed DEP, exaggerated allergic airway inflammation through the enhancement of T-helper type 2 responses. The coexistence of OC with carbonaceous nuclei caused the most remarkable aggravation. DEP components might diversely affect various types of respiratory diseases, while whole DEP might mostly aggravate respiratory diseases.

Effects of phenanthraquinone on allergic airway inflammation in mice.

BACKGROUND: Diesel exhaust particles (DEP) enhance allergic airway inflammation in mice (Takano et al., Am J Respir Crit Care Med 1997; 156: 36-42). DEP consist of carbonaceous nuclei and a vast number of organic chemical compounds. However, it remains to be identified which component(s) from DEP are responsible for the enhancing effects. 9,10-Phenanthraquinone (PQ) is a quinone compound involved in DEP. OBJECTIVE: To investigate the effects of PQ inoculated intratracheally on allergic airway inflammation related to ovalbumin (OVA) challenge. MATERIALS AND METHODS: We evaluated effects of PQ on airway inflammation, local expression of cytokine proteins, and allergen-specific immunoglobulin production in mice in the presence or absence of OVA. Results In the presence of OVA, PQ (2.1 ng/animal) significantly increased the numbers of eosinophils and mononuclear cells in bronchoalveolar lavage fluid as compared with OVA alone. In contrast, the numbers of these cells around the airways were not significantly different between OVA challenge and OVA plus PQ challenge in lung histology. PQ exhibited adjuvant activity for the allergen-specific production of IgG1 and IgE. OVA challenge induced significant increases in the lung expression of IL-4, IL-5, eotaxin, macrophage chemoattractant protein-1, and keratinocyte chemoattractant as compared with vehicle challenge. However, the combination of PQ with OVA did not alter the expression levels of these proteins as compared with OVA alone. CONCLUSION: These results indicate that PQ can enhance the immunoglobulin production and the infiltration of inflammatory cells into alveolar spaces that are related to OVA, whereas PQ seems to be partially responsible for the DEP toxicity on the allergic airway inflammation.

Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model.

BACKGROUND: Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. OBJECTIVE: The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. METHODS: C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5 mg/mouse/day). RESULTS: Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. CONCLUSION: These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody.

Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: relation to inflammatory activity.

Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1beta and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.