• Toxicological Research
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• v.17
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• pp.305-307
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• 2001

Toluene diisocyanate (TDI) is widely used in the manufacture of polyurethanes and is a recognized cause of occupational asthma. Although extensive investigations have been undertaken, the molecular mechanism(s) of the disease is still unclear. We hypothesized that inflammatory cytokines are required during both the sensitization and elicitation phases of the disease and have utilized TNF-R knock-out (KO) mice to address the hypothesis. Black C57 TNFR knock-out mice were exposed to TDI by sc injection and challenged by inhalation of 100 ppb TDI vapor. Control animals included: wild type C57 animals, sham-exposed animals that were challenged with TDI, and animals that were injected with anti-TNF antibodies prior to sensitization and again prior to challenge. Total IgE was increased in the knock-out animals compared with the wild type sensitized and challenged animals whereas TDI-specific IgG antibodies did not differ significantly in KO and wild type animals. There was less inflammation in the nares and trachea in KO animals compared with the wild type animals exposed to TD1 as well as less goblet cell hyperplasia and epithelial damage. Airway reactivity was assessed in animals treated with anti-TNF$\alpha$ antibody and found to be substantially reduced compared with that in sensitized and challenged animals. These results indicate that TNF$\alpha$ plays a role in the immunologic and physiologic responses and in airways inflammation in this animal model and suggests a role for TNF in occupational asthma due to TDI.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.425-433
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• 2004

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.

• Parasites, Hosts and Diseases
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• v.28 no.1
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• pp.45-52
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• 1990

Intestinal histopathological changes due to infection with Echinostcma hortense (Trematoda) were studied in rats after experimental infection with the metacercariae. The metacercariae were obtained from the tadpoles of Rana nigrcmaculata, a second intermediate host infected in the laboratory. Total 18 albino rats(Sprague-Dawley) were given 200 matacercariae each and sacrificed on the day 1, 3, 7, 11, 22 or 44 post-infection(PI) Segments of- the small intestine at 1, 3, 5, 8 and 30 cm posterior to the pylorus(PTP) were rejected and studied histopathologically. 1. The flukes were seen to have intruded into the intervillous space in the upper small intestine at early stages(1∼3 days PI), however, they were located mainly in the intestinal lumen at later stages(7∼44 days PI) . The flukes were sucking and destroying the epithelial layers of villi with their oral and ventral suckers. 2. Histopathological changes of the intestine were recognizable in as early as 1∼3 days after infection, and the changes became severer as the infection progressed. 3. The intestinal mucosa was histopathologically characterized by villous atrophy and crypt hyperplasia throughout the infection period. Major villous changes were blunting, fusion, severe destruction and loss of epithelial layers of villi. Villous/crypt(V/C) height ratio was remarkably reduced from 3 : 1 in controls to 1 : 1 in severely infected animals. In the stroma of villi, inaamma- tory cell infiltrations, vascular congestion, edema, and/or fibrosis were recognized. The goblet cells were increased in number after 11 days PI. It was revealed in the present study that the pathological changes in the intestine of rats infected with E. hortense were chieay confined to the mucosal layer of the upper small intestine, however, the changes were very severe accompanying remarkable destruction of villi and loss of mucosal integrity, and persistent until 44 days PI.

• Microbiology and Biotechnology Letters
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• v.36 no.4
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• pp.343-352
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• 2008

Frankincense, the gum resin derived from Boswellia species, is complex mixtures composed of about $5{\sim}9%$ highly aromatic essential oil, $65{\sim}85%$ alcohol-soluble resins, and the remaining water-soluble gums. The anti-inflammatory properties of frankincense, alcohole-soluble resins, are well-recognized, but the question of whether aromatic essential oil also plays a role in the allergic asthma remains unanswered. This study was performed to evaluate anti-inflammatory effects of Boswellia sacra essential oil (BSEO) on ovalbumin (OVA)-induced asthma mouse model. BALB/c mice after intraperitoneal OVA sensitization were challenged with intratracheal OVA. One experimental group was inhaled with 0.3% BSEO for the later 8 weeks. BALB/c mice were sensitized and challenged with OVA and developed airway eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. In contrast, the BSEO treated mice had reduced a number of eosinophils among BALF cells, goblet cell hyperplasia, and airway hyperresponsiveness. Cytokine analysis of BALF revealed that BSEO caused an increase in Th1 cytokine (interferon-$\gamma$ (IFN-$\gamma$)) and a decrease in Th2 cytokines (interleukin-4 (IL-4), IL-5 and IL-13) levels. In addition, the OVA-specific serum IgE and eotaxin levels were also reduced. In mice inhaled BSEO, $CD4^+$, $CD3^+/CCR3^+$, and $B220^+/CD23^+$ mediastinal lymph nodes cells were also decreased. These results suggest that inhaled BSEO as a immunomodulator in Th1/Th2 mediated asthma may have therapeutic potential for the treatment in allergic airway inflammation by a simple, cost-effective way.

• Journal of Life Science
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• v.17 no.2 s.82
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• pp.248-253
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• 2007

This research investigated whether exposure of diesel exhaust particulate (DEP) and particulate matter (PM) effects on airway remodeling in asthma induced Balb/c and IL-10 knock out (KO) mouse. Mice were sensitized with intraperitoneal injection with ovalbumin, followed by challenges with intranasal ovalbumin. After that mice placed in inhalation chamber and exposed to DEP and $PM(10\;mg/m^3)$. The evidence of airway remodeling was assessed by masson's trichrome staining and PAS staining. The stainability of masson's trichrome and PAS reaction were increased in asthma-induced Baltic mice groups compared with control mice groups. More intensive stainability for masson's trichrome and PAS were appeared in the asthma-induced DEP and PM-exposed groups than asthama-induced groups. But, not significantly increased subepithelial fibrosis and the nember of goblet cell hyperplasia in asthma-induced IL-10 KO mice groups and asthma-induced+DEP and PM-exposed IL-10 KO mice than IL-10 KO mice groups. These results indirectly suggesting that exposure to DEP and PM in asthmatic patients might be aggravate clinical symptoms and IL-10 which seems to play a central role in allergic asthma. In conclusion, DEP and PM exposure might have additive effects on the ovalbumin- induced asthma in a murine model.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.543-552
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• 2004

Background : Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. Methods : Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs($30{\mu}g$) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. Results : The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. Conclusion : CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.