• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.207-213
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• 2016

Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.577-583
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• 2002

Experimental studies were done to research the Clinical effects of Insambakhab-tang on the Anti-allergic effect and pulmonary function of O₃ intoxicated Mice. Anti-allergic effect experiment consisted of vascular permeability responses to intradermal histamine and serotonin, 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, and delayed type hypersensitivity responses to Picryl Chloride and SRBC. Pulmonary function of O₃ intoxicated Mice experimental consisted of pulmonary thromboembolism (Sodium Arachidonate-induced and ADP-induced), lung TBA value, and serum Na/sup +/, K/sup +/, Cl/sup +/ level. The results obtained as follows; 1. In the effects of Insambakhab-tang on the pulmonary thromboembolism by Sodium Arachidonic acid and ADP, Insambakhab-tang group revealed significant effect. 2. In the effects of Insambakhab-tang on the vascular permeability responses to intradermal histamine, Insambakhab-tang group revealed significant effect. 3. In the effects of Insambakhab-tang on the vascular permeability responses to intradermal serotonine, Insambakhab-tang group revealed significant effect. 4. In the 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, Insambakhab-tang group revealed significant effect. 5. In the delayed type hypersensitivity responses to Picryl Chloride, Insambakhab-tang group revealed significant effect. 6. Insambakhab-tang group revealed significant effect on decrease of the lung TBA value of lung. 7. In the effects of Insambakhab-tang on Serum Na/sup +/, K/sup +/ Level in O₃-intoxicated Mice. Insambakhab-tang group revealed none significant effect, but In the effects of Insambakhab-tang on Serum Cl/sup +/ Level in O₃-intoxicated Mice, Insambakhab-tang group revealed significant effect.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.273-278
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• 1995

The effect of methamphetamine on the pulmonary metastasis was investigated in C57BL/6 mice injected with Bl6 melanoma cells. Bl6 melanoma cells (2$\times$10$^{5}$ cells) were injected intravenously into 5~7 weeks old C57BL/6 mice. Mice were then treated intraperitoneally with methamphetamine either acutely (two times with one week interval) or subchronically (daily for 14 days). Degree of pulmonary metastasis was investigated and specific immunologic parameters such as natural killer cell cytotoxicity(NKCC), antibody-dependent cellular cytotoxicity(ADCC) and blastogenic responses of splenocytes were examined. Mice which had been subchronically treated with methamphetamine showed significant decreases in the number of pulmonary metastasis of Bl6 melanoma cells, NKCC and ADCC without a significant change in blastogenic responses. In the acutely-treated group, slight trends of decrease in the numbers of pulmonary metastasis, NKCC and ADCC were observed without statistical significances whereas there was a significant increase in blastogenic responses. The mechanism underlying the decrease in the degree of metastasis despite diminished NKCC and ADCC after methamphetamine treatment and the relationship between the degree of pulmonary metastasis and duration of methamphetamine treatment remain to be investigated.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.321-328
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• 1999

Pulmonary blood vessels with diameters of $200{\sim}400\;{\mu}m$ produce considerably more force in response to vasoconstrictor drugs than those which are either smaller or larger. We have therefore investigated whether or not hypoxic pulmonary vasoconstriction (HPV) is more powerful in vessels of these diameters. We have also looked at the possibility that vessels from different regions of the lung respond differently. To do this we have grouped vessels according to their location within the lung as well as by size. We used a small vessel myograph (Cambustion AM10, Cambridge, UK) to study 208 preconstricted $(1\;{\mu}M\;PGF_{2{\alpha}})$ small pulmonary arteries $(300{\sim}800\;{\mu}m$ diameter when stretched to a tension equivalent to 25 mmHg transmural pressure) from 39 rats anaesthetized with 2% inspired halothane. A biphasic contraction was observed in response to hypoxia (ca. 25 mmHg $Po_2).$ The magnitudes of both the first, transient, phase (PT, peak tension) and of the second, sustained, phase (SST, steady state tension) were measured. The latter was measured 40 min after the start of hypoxia. The first phase was most pronounced in vessels with an average diameter of 423 ${\mu}m$ while the second phase was most pronounced in larger vessels (mean diameter 505 ${\mu}m).$ These maximal responses were all seen in vessels somewhat larger than reported by others. The responses of smaller vessels $(400{\sim}500\;{\mu}m)$ did not depend upon their location within the lung, but those of larger vessels $(600{\sim}700\;{\mu}m)$ showed regional differences. Those from the right lobe and those from the base of the lung gave the largest responses. It was especially noticeable that large vessels (631 ${\mu}m$ diameter) from the base of the right lung gave the biggest responses. Thus HPV seems to occur not in a uniform manner, dependent solely to the size of vessels, but it also depends to some degree on the region of the lung from which vessels have been taken. Furthermore, our results suggest that larger vessels, as well as smaller ones, may contribute significantly to HPV.

• YAKHAK HOEJI
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• v.37 no.6
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• pp.605-614
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• 1993

To investigate the endothelial dependence of angiotensin II(A II)-induced responses in the systemic and pulmonary arterial system of acute renal hypertensive rats of 2-kidney, 1-ligation type (RHRs), A II-induced vasocontractile and pressor effects were evaluated in isolated arteries and in vivo, respectively. A II dose-dependently contracted intact thoracic aorta and pulmonary artery (E$_{max}$:40% at 10$^{-7}$M and 80% at 3$\times$10 $^{-8}$M, respectively) from normotensive rats(NRs), which was significantly increased by removal of endothelial cells or pretreatment with EDRF inhibitors. In NRs, A II increased mean systemic and pulmonary arterial pressure(33 and 5.6mmHg at 0.1 $\mu\textrm{g}$/kg, respectively), the effect being significantly increased (P<0.01) by L-NAME(30mg/kg, i.v.). However, A II-induced contraction of intact thoracic aorta and pulmonary artery(E$_{max}$: 33% at 10$^{-7}$M and 93% at 3$\times$10$^{-8}$M, respectively) from RHRs were not changed after endothelial function was disrupted as above; similarly, pressor effects of A II on the systemic and pulmonary arterial pressure in RHRs did not altered by L-NAME. A II tachyphylactic responses for intact thoracic aorta from NRs and RHRs(65 and 87% at 10$^{-8}$M, respectively) were greater than those for pulmonary artery(19 and 19% at 10$^{-8}$M, respectively). Distruption of endothelial function significantly (P<0.01) depressed A II tachyphylaxis for thoracic aorta, but not for pulmonary artery. These results suggest that vascular reactivity to A II is not altered in RHRs, and it is greater for pulmonary arterial system than for systemic arterial system. A II reactivity is EDRF-dependent in both arterial systems of NRs, but EDRF-independent for RHRs. Finally, EDRF is one of the major factors underlying A II tachyphylaxis for thoracic aorta, but not for pulmonary artery.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.183-189
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• 1999

This investigation is to determine whether the surface complexation of iron influence acute pulmonary responses induced by silica. For this study, three varieties of cation complexed silica were used: $silica-H^+,\;-Zn^{2+},\;and\;-Fe^{3+},$ since the first two are not active in the transport of electrons and generate little free radicals relative to the dust with the surface iron. Rats (270 to 280 g) were intratracheally (IT) instilled with saline, $silica-H^+,\;-Zn^{2+},\;or\;-Fe^{3+}$(5 mg in 0.5 ml saline). After 4 h, cell number, type, and differentiation were analysed in the bronchoalveolar lavage cells, and the levels of lactate dehydrogenase (LDH) and total protein were determined in the lavage fluid. In addition, bronchoalveolar lavage cells were cultured, and nitric oxide production was measured using nitrate assay. Inducible nitric oxide synthase (iNOS) mRNA in the bronchoalveolar lavage cells was also determined by northern blot analysis. Differential counts of the lavage cells showed that red blood cells were increased by 9-, 8-, and 13-fold and total leukocytes (lymphocytes plus polymorphonuclear neutrophils) by 48-, 36-, and 33-fold, following IT $silica-H^+,\;-Zn^{2+},\;and\;-Fe^{3+},$ respectively compared with the saline group. Meanwhile, there were no significant differences in red blood cells and total leukocytes among any of the cation complexed silica groups. The levels of LDH and total protein in the lavage fluid were significantly increased by 3- to 4-fold. However, compared among these silica groups, $Fe^{3+}$? complexation did not significantly change the LDH activity and total protein. NO production in cultured bronchoalveolar lavage cells was elevated by 2-fold, following IT any of the silica treatments compared with the saline group. Furthermore, the steady-state levels of iNOS mRNA in the lavage cells were greatly increased. There were any differences in iNOS mRNA expression among the silica-treated groups as with NO production. These findings suggest that surface complexed iron may not influence the acute pulmonary responses resulted from 4h exposure to silica.

• The Journal of Pediatrics of Korean Medicine
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• v.12 no.1
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• pp.231-256
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• 1998

Experimental studies were done to research the clinical effects of Chihyosan and Chihyosangamibang on the Anti-allergic effect and pulmonary function of $O_3$ intoxicated Rats. Anti-allergic effect experiment consisted of vascular permeability responses to intradermal histamine and serotonin, 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, and delayed type hypersensitivity responses to Picryl Chloride and SRBC. Pulmonary function of $O_3$ intoxicated Rats experiment consisted of lung TBA value, water Contents of the lung, oxygen consumption time, and arterial blood $pCO_2,\;pO_2,\;HCO_3^-$, pH level. The results obtained as follows; 1. In the effects of Chihyosan and Chihyosangamibang on vascular permeability responses to intradermal histamine, both of chihyosan and Chihyosangamibang group revealed significant effect. 2. In the effects of Chihyosan and Chihyosangamibang on vascular permeability responses to intradermal serotonin, both of chihyosan and Chihyosangamibang group revealed significant effect. 3. In the 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, Chihyosan groups revealed significant effect, but Chihyosangamibang groups revealed none significant effect. 4. In the delayed type hypersensitivity responses to Picryl Chloride, Chihyosan and Chihyosangamibang groups revealed none significant effect. 5. In the delayed type hypersensitivity responses to. SRBC, Chihyosan revealed none significant effect, but Chihyosankamibang revealed significant effect. 6. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of the lung TBA value of lung. 7. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of the water contents of right and left lung. 8. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of oxygen consumption time. 9. In the decrease effect of arterial blood $pCO_2$ level, both of Chihyosan and Chihyosangamibang groups revealed none significant effect. 10. In the increase effect of arterial blood $pO_2$ level, both of Chihyosan and Chihyosangamibang groups revealed none significant effect. 1. In the decrease effect of arterial blood $HCO_3^-$ level, both of Chihyosan and Chihyosangamibang groups revealed significant effect. 12. In the increase of arterial blood pH level, Chihyosangamibang groups revealed none significant effect, but Chihyosan groups revealed significant effect. According to above stated results, both of Chihyosan and Chihyosangamibang are very usefully for treatment of cough, asthma, chronic obstructive pulmonary diseases and allergic pulmonary diseases.

• Tuberculosis and Respiratory Diseases
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• v.76 no.4
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• pp.169-174
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• 2014

Background: The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. Methods: Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. Results: From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. Conclusion: The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD.

• Molecules and Cells
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• v.41 no.8
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• pp.762-770
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• 2018

Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced $I{\kappa}B{\alpha}$ degradation, $NF-{\kappa}B$ nuclear translocation, and $TNF-{\alpha}$ production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced $I{\kappa}B{\alpha}$ degradation, and heated gAd was unable to degrade $I{\kappa}B{\alpha}$, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative $IKK{\beta}$ ($DN-IKK{\beta}$) or DN-Akt overexpression blocked gAd-induced $I{\kappa}B{\alpha}$ degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the $I{\kappa}B/NF-{\kappa}B$ and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the $I{\kappa}B/NF-{\kappa}B$ pathway, and IRAK-1 downregulation, respectively.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.109-114
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• 2010

The molecular mechanisms involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) are poorly defined. Accumulating evidences indicate that chronic inflammatory responses and adaptive immunity play important roles in the development and progression of the disease. Recently, it has been shown that IL-17 producing CD4 T cells, named Th17 cells, which have been implicated in the pathogenesis of several inflammatory and autoimmune diseases, are involved in airway inflammation and COPD. In addition, we and others suggest that autoimmunity may play a critical role in the pathogenesis of COPD. Here, we will review the current understanding of roles of Th17 cells and autoimmune responses in COPD.