• Korean Journal of Bronchoesophagology
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• v.4 no.1
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• pp.64-72
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• 1998

This study aimed at observing the effect of diazepam on the contractility of trachealis muscle isolated from canine trachea, possible involvement of central or peripheral type benzodiazepine receptor, and the calcium related mechanism of action of diazepam. Trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiologic salt solution maintained at $37^{\circ}C$, and aerated with 95% $O_2$ /5% $CO_2$. Isometric myography was performed. Diazepam reduced the basal tone concentration dependently, and this inhibitory action was not affected by neither flumazenil, a central benzodiazepine receptor antagonist, nor PK11195, a peripheral benzodiazepine receptor antagonist. Pretreatment with diazepam showed the inhibitory effect on the concentration-response curves to agonists such as bethanechol, 5-hydroxytryptamine and histamine. Diazepam also caused concentration-related inhibition of contraction with potassium chloride 30 mM. The effect of diazepam on the basal tone and potassium chloride-induced contraction with calcium channel blockers were compared. Similar results were obtained in canine trachealis with verapamil, nifedipine and diltiazem. These results suggest that diazepam relax an airway muscle not via specific receptors but by a similar action as calcium channel blockers in canine trachealis muscle.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.12a
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• pp.3-13
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• 2020

Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium causing serious infections. The P. aeruginosa T3SS is a syringe-like apparatus on the bacterial surface, with 4 effector toxins: ExoS, ExoT, ExoY, and ExoU. Here, we investigated the effect of ExoS and ExoT of the T3SS of P. aeruginosa K strain (PAK). The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. PAK clinical strains induce proinflammatory cytokine production through the T3SS, and this involves NF-κB activation in pneumonia mouse models. We tried to confirm the role of the NF-κB transcription factor in ExoS- and ExoT-induced pneumonia mouse models. pro-inflammatory cytokines induction in response to ExoS and ExoT infection relied on NF-κB activation. Our findings highlight the roles of natural poduct in inhibiting proinflammatory cytokine expression during ExoS and ExoT exposure in PAK infections, paving the way for a novel therapeutic approach for the treatment of pulmonary infections.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.427-438
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• 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

• The Journal of Internal Korean Medicine
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• v.17 no.1
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• pp.210-217
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• 1996

Farfarae Flos, a traditional herb medicine, has been used in Korea and China for many centuries as a treatment for respiratory disease. The purpose of the present study was to determine the effect of Farfarae Flos on histamine-induced tracheal smooth muscle contraction in rats. Guinea pigs(500g, female) were killed by CO2 exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine which evoked 50% of maximal response (ED50) was obtained from cumulative dose response curves for histamine (10-7-10-4M). Contractions evoked by histamine(ED50) were inhibited significantly by Farfarae Flos. The mean percent inhibition was 8.7% after 1.5mg/ml Farfarae Flos, and 33.5% (p<0.05) after 5.0mg/ml Farfarae Flos. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Farfarae Flos. Following treatment with propranolol, the mean percent inhibition caused by 5.0mg/ml Farfarae Flos. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Farfarae Flos. These results indicate that Farfarae Flos can relax histamine-induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves, in part, symphathetic nerve system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.322-326
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• 2002

Artemisia iwayomogi has been used in Korea for many centuries as a treatment for anemia. The effect of Artemisia iwayomogi on tracheal smooth muscle is not known. The purpose of the present study is to determine the effect of Artemisia iwayomogi on histamine induced tracheal smooth muscle contraction in guinea pigs. Guinea pigs(500g, male) were killed by CO₂ exposure and a segment (8-10mm) of the thoracic trachea from each rat and guinea pig was cut into equal segments and mounted ‘in pairs’ in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine (His) which evoked 50% of maximal response (ED/sub 50/) was obtained from cumulative dose response curves for histamine (10/sup -7/～10/sup -4/M). Contractions evoked by His (ED/sub 50/) were inhibited significantly by Artemisia iwayomogi. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 31.9% (p<0.05) after 100㎕/㎖ Artemisia iwayomogi. L-NNA slightly but significantly attenuated the inhibitory effects of Artemisia iwayomogi. Following treatment with L-NNA, the mean percent inhibition caused by 100㎕/㎖ Artemisia iwayomogi fell to 44.6% in guinea pig induced by histamine contraction. Propranolol, indomethacin and methylene blue did not significantly alter the inhibitory effect of Artemisia iwayomogi. These results indicate that Artemisia iwayomogi can relax histamine induced contraction of guinea pig, and that this inhibition related to nitric oxide formation.

• Korean Journal of Acupuncture
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• v.17 no.1
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• pp.67-73
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• 2000

The purpose of the present study is to determine the effect of Radix Stemonae on histamine induced tracheal smooth muscle contraction in guinea pigs. Guinea pig(500g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine (His) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine ($10^{-7}∼10^{-4}M$). Contractions evoked by His ($ED_{50}$) were inhibited significantly by Radix Stemonae. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 87.4% (p<0.01) after $100{\mu}l/ml$ Radix Stemonae. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Radix Stemonae fell to 16.2% in guinea pig induced by histamine contraction. Indomethacin and methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Radix Stemonae. These results indicate that Radix Stemonae can relax histamine induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves sympathetic effects.

• The Journal of Internal Korean Medicine
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• v.18 no.2
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• pp.83-93
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• 1997

Rhizoma Coptidis, a traditional herb medicine, has been used in Korea and China for many centuries as a treatment for many disease. The purpose of the present study was to determine the effect of Rhizoma Coptidis on histamine-induced tracheal smooth muscle contraction in guinea pigs and rats. Guinea pigs(500g, male) and rats(250g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine ($10^{-7}-10^{-3}M$). Contractions evoked by histamine($ED_{50}$) were inhibited significantly by Rhizoma Coptidis. The mean percent inhibition was 33.2% after 1.5mg/ml Rhizoma Coptidis, and 69.5% after 5.0mg/ml Rhizoma Coptidis in guinea pigs, and the mean percent inhibition was 25.3% after 1.5mg/ml Rhizoma Coptidis, and 65.8% after 5.0mg/ml Rhizoma Coptidis in rats. Indomethacin ($10^{-7}M$) slightly but significantly attenuated the inhibitory effects of Rhizoma Coptidis. But propranolol and methylene blue ($10^{-7}M$) did not significantly alter the inhibitory effect of Rhizoma Coptidis. These results indicate that Rhizoma Coptidis can relax histamine-induced contraction of guinea pig and rat tracheal smooth muscle, and that this inhibition involves, in part, cyclooxygenese inhibitor.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.294-312
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• 2023

Objective: The purpose of this study is to evaluate the effects of GGX on an ovalbumin (OVA)-induced asthma mice model. Methods: Balb/c mice were challenged with OVA and then treated with three concentrations of GGX (100, 200, and 400 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lungs of the mice were analyzed by fluorescence-activated cell sorting, ELISA, real-time PCR, H&E, Masson's trichrome, PAS and AB-PAS staining, and immunohistofluorescence staining. Results: GGX significantly inhibited the increase of total cells, immune cells (lymphocyte, neutrophils, macrophage, CD4+, CD8+, CD4+CD69+, CD62L-CD44high+, Gr-1+SiglecF-), and the expression of cytokines (IL-4, IL-5, IL-13, IFN-γ) in BALF. It also significantly inhibited the increase of total cells, immune cells (lymphocyte, neutrophils, eosinophil/macrophage, CD3+, CD19+, CD3+CD193+, CD4+, CD8+, CD4+CD69+, CD62L-CD44high+, and Gr-1+SiglecF-), and the expression of IL-13, TARC, and MCP-1 in lung tissue. GGX decreased the severity of histological lung injury and the expressions of STAT3 and GATA3. Conclusion: This study suggests the probability of using GGX for the treatment of asthma by inhibiting inflammatory immune response.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.19 no.2
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• pp.128-132
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• 2008

Background: Laryngeal contact granuloma is an inflammatory hypertrophic granulation tissue arising at around the vocal process of arytenoid cartilage. Various approaches are currently used for the treatment, but a solid guideline has not been established. Objectives: We aimed to compare the each treatment modality in the hope of suggesting a guideline for the successful management of laryngeal contact granuloma. Method: Eighty-seven treatment cases of 56 patients were analyzed. Cases having recent intubation history were excluded from the study. All patients received vocal hygiene education. Proton pump inhibitors (PPI, N = 33) or H2 receptor antagonists ($H_{2}RA$, N =26) were used as a first-line treatment. Among the non-responders to $H_{2}RA$, 11 cases received PPI as a second-line therapy. Eight cases received botulinum toxin injection and 9 cases had laryngomicrosurgical removal. Results: As an initial therapy, response rate to PPI and $H_{2}RA$ was 60.6% and 38.5% respectively, which was not statistically different (p=0.091). Response rate of PPI as the second-line therapy was 36.3% (p=0.162 when compared to that of first-line PPI therapy). Response rate of Botulinum toxin injection was 75%. All cases of surgical removal recurred in a relatively short period (mean 1.9months). Conclusion: In patients having laryngeal contact granuloma, combined therapy with vocal hygiene education and PPI medication would provide more than 60% of therapeutic response. Botulinum toxin injection is highly effective even in non-responders to antireflux therapy. The only indications of surgery are to resolve diagnostic doubt or to treat acute airway compromise.

• BMB Reports
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• v.48 no.3
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• pp.178-183
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• 2015

Dendritic cells play an important role in determining whether na${\ddot{i}}$ve T cells mature into either Th1 or Th2 cells. We determined whether heat-shock protein X (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-${\beta}$ production and T-bet gene expression but reduced IL-13 production and GATA-3 gene expression. HspX also inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of regulatory T cells in the mediastinal lymph nodes. This study provides evidence that HspX plays critical roles in the amelioration of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of HspX with respect to its effects on a murine model of asthma.