Repeated instillations of Dermatophagoides farinae into the airways can induce Th2-dependent airway hyperresponsiveness, eosinophilia and remodeling in mice

Wakahara, Keiko; Tanaka, Hiroyuki; Takahashi, Go; Tamari, Mayumi; Nasu, Reishi; Toyohara, Tatsuyuki; Takano, Hirohisa; Sakai, Saburo; Inagaki, Nobuya; Shimokata, Kaoru; Nagai, Hiroichi

doi:10.1016/j.ejphar.2007.09.005

Cited by 23 publications

(19 citation statements)

References 44 publications

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“…Thus, DEP are thought to play an important role in the induction of this mRNA in DE. Furthermore, the production of TGF-β 1 is partially dependent on Th2 responses (18,30) and/or eosinophils (33,34). These findings suggest that the synergistic effect of the action of DEP upon bronchial epithelial cells and antigen-induced Th2 responses cause the increase of TGF-β 1 levels in the BALF, leading to the aggravation of allergen-induced subepithelial fibrosis.…”

Section: Discussionmentioning

confidence: 67%

“…As described above, using a 10-fold magnification objective, 3 representative areas were chosen, avoiding the selection of the furcation of the bronchus and the surrounding blood vessels in the largest airway. Subsequently, with a 40-fold magnification, epithelial basement membrane areas ≥250 μ m were selected, and the thickness of the epithelial layer and the fibrotic area (stained in blue) 30 μ m beneath the basement membrane of the standardized sampling points were measured (18). The means of the thickness of the epithelial layer and fibrotic area divided by basement membrane length were calculated for 8 -9 mice.…”

Section: Histological Studymentioning

confidence: 99%

“…Recently, we (17,18) have established a mouse model for allergic asthma using a major allergen, Der f. This mouse model is characterized by eosinophil infiltrates into the airways, increases in the level of interleukin (IL)-13, decrease in the level of interferon-γ (IFN-γ ) in the bronchoalveolar lavage fluid (BALF), AHR to acetylcholine (ACh), and increases in the serum allergenspecific immunoglobulin (Ig) G1 level by repetitive intratracheal administration of the allergen without a T helper type 2 (Th2)-skewing adjuvant. Furthermore, airway remodeling, characterized by severe goblet cell hyperplasia/hypertrophy, subepithelial fibrosis, and increases in the level of TGF-β 1 in the BALF were also demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

et al. 2010

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Abstract. Recent research has focused on the effects of ambient particulate pollution and much evidence has indicated that particulate pollution is associated with the onset of asthma and allergy; however, the effect of diesel exhaust particles (DEP) on the development of allergen-induced airway remodeling has not been fully investigated in vivo. In the present study, we examined the effects of DEP on Dermatophagoides farinae allergens (Der f)-induced asthma-like phenotypes in mice. Mice were administered i.t. 8 times with Der f. DEP were injected i.t. with Der f 4 times throughout the experiment or twice at the sensitization period. In both cases, DEP aggravated Der f-induced increases in airway responsiveness to acetylcholine, the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), serum Der f-specific IgG1 levels, Th2 cytokines and transforming growth factor-β 1 levels in BALF, and amount of hydroxyproline in the right lungs. Furthermore, goblet cell hyperplasia and subepithelial fibrosis were also markedly aggravated. These findings indicate that DEP can potentiate airway remodeling induced by repeated allergen challenge as well as Th2-drived airway hyperresponsiveness, eosinophilic inflammation, and IgG1 production and that DEP can exhibit adjuvant activity for airway remodeling, probably due to the enhancement of allergen sensitization and/or of Th2 polarizing pathways.

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Section: Discussionmentioning

confidence: 67%

Section: Histological Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

et al. 2010

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“…It may be necessary to develop another late asthmatic model that can be developed by intratracheal administration of an antigen at a low dose for the long term. In addition, in order to further mimic the pathogenesis, natural antigen contaminated with endotoxin is also indispensable for an ideal model of experimental asthma, as indicated by the literature (34,35).…”

Section: Effects Of Anti-il-5 Mab On the Development Of Airway Remodementioning

confidence: 99%

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Nabe¹,

Morishita²,

Matsuya³

et al. 2011

J Pharmacol Sci

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Abstract. It is known that the late asthmatic response (LAR), a characteristic feature of asthma, is closely associated with CD4 + Th2 cell-mediated allergic inflammation. Airway remodeling is also a pathogenesis of asthma, but literature reporting roles of CD4 + cells in the remodeling is controversial. There has been no study that simultaneously assessed the roles of CD4 + cells in both LAR and airway remodeling. Sensitized mice were intratracheally challenged with ovalbumin 4 times. Treatment with an anti-CD4 monoclonal antibody (mAb) before the 1st challenge almost completely abolished increase in CD4 + cells in the tissues after the 4th challenge. The late phase increase in airway resistance after the 4th challenge was also completely inhibited by anti-CD4 mAb. Parameters of airway remodeling, subepithelial fibrosis and epithelial thickening were attenuated by treatment, whereas the inhibition was only 30% -40%. Bronchial smooth muscle thickening was not affected. Because interleukin (IL)-5 production as well as eosinophilia was effectively suppressed by anti-CD4 mAb, the effect of anti-IL-5 mAb was also examined, resulting in no inhibition of airway remodeling. Collectively, although the LAR was completely dependent on CD4 + cell activation, airway remodeling was only partially dependent on the cell.

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“…Until now, it is reported that the decrease of eosinophil numbers in BALF was correlated with attenuation of asthma symptoms in animal models. 15,25) Many clinical studies have also documented a correlation between pulmonary eosinophilia and asthma, and the degree of eosinophils in BALF correlates with disease severity. 26) Thus, pulmonary eosinophilia has been closely related to asthma symptoms.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma

Asano

Kumakura

Taki

et al. 2010

Biological & Pharmaceutical Bulletin

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Bronchial asthma has clinical manifestations, which include variable degrees of airflow obstruction, airway hyperresponsiveness, and airway inflammation.1) The inflammatory process in asthma is dominated by T helper-2 (Th2) cells which produce interleukin-4 (IL-4), IL-5, and IL-13. 2)Thalidomide was synthesized in 1954 by CIBA Pharmaceutical Company, and prescribed as a sedative, tranquiliser, and antiemetic for morning sickness. Because the highest risk for teratogenicity arose when the drug was taken between weeks 3 and 8 after conception, it was withdrawn from many countries including Japan. However, the drug was revived as an effective treatment for erythema nodosum leprosum lesions in 1965. The U.S.A. Food and Drug Administration approved it for this indication in 1998. 3)Thalidomide, which is metabolized by cytochrome P450, 3,4) has a wide range of pharmaceutical and biological activities. Currently, clinical investigations of thalidomide have been conducted in patients with diverse diseases, including multiple myeloma, rheumatoid arthritis, and human immunodeficiency virus infection. 5,6) The beneficial pharmacological effects elicited by thalidomide include anti-angiogenic, anti-viral, anti-inflammatory, and immunomodulatory activities, 5,7) although the precise mechanisms are unknown.8)It has been reported that thalidomide administered with albendazole suppressed eosinophilic infiltration in cerebrospinal fluid in a murine vermination model. 9) However, little is known about the effect of thalidomide on the airway hyperresponsiveness and eosinophilic inflammation in allergic asthma.The purpose of this study was to investigate the effects of thalidomide on airway inflammation and hyperresponsiveness in a murine model of allergic asthma. We hypothesized that thalidomide would have anti-inflammatory effects in allergic asthma. MATERIALS AND METHODS Sensitisation and Challenge with OvalbuminSevenweek-old female BALB/c mice (SLC, Shizuoka) were purchased and maintained in our specific pathogen-free animal facility. The mice were maintained at room temperature (23Ϯ2°C) and humidity (55Ϯ10%) in an air-conditioned room. They were fed a standard laboratory diet and given water ad libitum. They were sensitised by an intraperitoneal injection with 100 mg ovalbumin (OVA) and 1 mg alum in 200 ml of phosphate-buffered saline (PBS) on day 0, and then by a hypodermic injection with 10 mg OVA in 20 ml of PBS on day 14. They were then placed in an acrylic chamber and challenged with 1% OVA for 10 min daily by a nebulizer (IS-2; Paris, Starnberg, Germany) between days 21 and 25. 10)Saline was used in place of OVA during the sensitisation and challenge stages of the protocol as a negative control. All protocols described in this study were approved by the Animal Ethics Committee of Nagoya University Graduate School of Medicine, Nagoya, Japan.Treatment Protocols For in vivo animal experiments, thalidomide (30, 100, or 300 mg/kg) was suspended in 0.5% carboxymethylcellulose, vortexed for 5 min, and administered orally via a ...

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Repeated instillations of Dermatophagoides farinae into the airways can induce Th2-dependent airway hyperresponsiveness, eosinophilia and remodeling in mice

Cited by 23 publications

References 44 publications

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma

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