• IMMUNE NETWORK
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• v.24 no.2
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• pp.3.1-3.23
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• 2024

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68⁺ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO^-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.169-182
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• 2002

Background: Allergic rhinitis(AR) is a heterogeneous disorder that despite its high prevalence is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. And it is frequently accompanied by symptoms involving the eyes, ears, and throat, including postnasal drainage. There are many different causes of rhinitis in children and adults. Approximately 50$\%$ of all cases of rhinitis are caused by allergy. In the case of rhinitis caused by allergens, symptoms arise as a result of inflammation induced by a gamma globulin E-mediated immune response to specific allergens such as pollens, molds, animal dander, and dust mites. The immune response involves the release of inflammatory mediators and the activation and recruitment of cells to the nasal mucosa. AR is similar to 鼻？, hypersensitive rhinitis in Oriental Medicine. I think hypersensitive rhinitis is including of AR, vasomotor rhinitis and non-allergic rhinitis related with eosinophil increased and so on. Purpose: To perform a clinical analysis of hypersensitive rhinitis including allergic rhinitis and estimate the efficacy of Oriental Medical treatment. Objective: We studied 96 patients who had visited our hospital with complaints of nasal symptoms from March 2000 to February 2002; they had the signs more than 2 - nasal obstruction, watery discharge, sneezing and eye or nasal itching. Parameters Observed & Methods: We treated them with acupuncture & herb-medication. Sometime they used aroma oil or external medicine. 1) the distribution of sex & age groups 2) the clinical type based on duration & the severity of symptom 3) the breakdown of complication & pasl history of Otolaryngologic or allergic disease 4) the clinical assessment and classification of rhinitis(sneezers and runners & blockers) 5) the associated symptoms and signs 6) the classification of Byeonjeung 7) the classification of prescriptions and 8) the efficacy of treatment. Result: 1. In the clinical type of based on duration, the intermittent type was 42.7$\%$ and the persistent was 57.3$\%$. 2. We observed the severity of symptoms based on the quality of life. The mild type was 24.0$\%$ and the moderate-severe was 76.0$\%$. 3. In the clinical assessment and classification of rhinitis, the sneezers and runners type was 69.8$\%$ and the blockers was 30.2$\%$. 4. The most common family history with otolaryngologic or allergic disease were allergic rhinitis(17.7$\%$), urticaria, paranasal sinusitis and T.B.(3.1$\%$). 5. The most common past history with otolaryngologic or allergic disease were paranasal sinusitis(14.6$\%$), atopic dermatitis and asthma(8.3$\%$). It was 31.3$\%$ they had a family history and 44.8$\%$, past history. 6. The most common complication was paranasal sinusitis(15.6$\%$). In decreasing order the others were otitis media with effusion(9.4$\%$), GERD and headache(6.3$\%$), asthma, bronchitis, nasal bleeding and allergic dermatitis(5.2$\%$). 7. Classification through Byeonjeung : ⅰ) 39 cases(34.9$\%$) were classified as showing Deficiency syndrome. The insuffficiency of Qi was 17.7$\%$, deficiency of Kidney-Yang, 12.5$\%$ and Lung-Cold, 10.4$\%$. ⅱ) 57 cases(59.4$\%$) were classified as showing Excess syndrome. The Fever of YangMing-meridian was 35.4$\%$, Lung-Fever, 24.0$\%$. 8. The efficacy of treatments showed: an improvement in 22cases(22.9$\%$); an improvement partly in 24 cases(25.0$\%$); no real improvement or changes in 16 cases(16.7$\%$); and couldn't check the results 18cases(18.6$\%$). Conclusion: We suggest that this study could be utilized as a standard of clinical Oriental Medical treatment when we treat hypersensitive rhinitis including allergic rhinitis.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.912-918
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• 2007

Purpose : Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. Allergic disease (AD), including atopic eczema, asthma, allergic rhinitis, and food allergy is characterized by an imbalance between cytokines produced by distinct T-helper cell subtypes. The aim of the study was to investigate the concentrations of cytokines and chemokines that were involved in allergic reactions in breast milk from allergic and nonallergic mothers and then analyse the effect of breastfeeding duration on the prevalence of allergic disease in the age of two. Methods : The breast milk samples were collected from mothers with AD (n=88) and without AD (n=47). Breast milk was collected at the second day (colostrum) and four weeks later (mature milk).The level of Interlukine (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, $TGF-{\beta}1$, $TGF-{\beta}2$, RANTES in breast milk were determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. Results : Mothers with AD had a higher concentration of IL-8 in colostrum compared with those without AD (P=0.021). But, $TGF-{\beta}1$ and $TGF-{\beta}2$ were higher concentrated in colostrum of mother without AD (P=0.013, P=0.001). Whereas concentrations of other cytokines were not significantly different between the two groups. There was no association between levels of cytokines and chemokines in the breast milk and allergic development during the first 2 years of life in the infants. Conclusion : The higher concentration of $TGF-{\beta}1$ and $TGF-{\beta}2$ in colostrum from non-allergic mothers may explain the protective effect. But, the higher concentrations of IL-8 in colostrum from allergic mothers may in part explain the controversial results on the protective effect of breastfeeding against allergic diseases. We conclude that there is no convincing evidence form a relation between cytokines in breast milk and allergic diseases in infants. Longer follow-up are necessary to evaluate the effects of breast milk components on AD.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.248-261
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• 1994

Background: Lectins are proteins or glycoproteins of non-immune origin that recognize a specific sequence of sugar residues. The availability of a large number of lectins has provided the capacity to identify selectively glycoconjugates possessing distinctive chemical structure in diverse sites of highly specialized biological activity. The purpose of the present study was to investigate the lectin binding patterns of various components in human pulmonary tubercles. Method: Biopsy specimens of tuberculous lung were obtained from male adult patients who underwent a surgical resection for severe pulmonary tuberculosis. The specimens were processed and stained with 13 kinds of biotinylated lectins according to some modification of Hsu and Raine's methods. Results: 1) In the caseous necrotic lesions, BS $I-B_4$ showed negative reaction and BS I were also negative except some irregularly-shaped cells located in the marginal zone. All other lectins, however, showed a positive reaction with various binding patterns. 2) The epithelioid cells were broadly divided into three groups according to the reaction patterns in the cytoplasms and cell membranes. 3) WGA, ECL, PHA-L, PHA-E and LCA showed strong staining in the lymphocytes. 4) SBA showed a different binding patterns between the endothelial layers located in the region beyond the fibrous layers and those located within the fibrous layers. 5) PNA showed a positive reaction in the outer 1/3 to 1/2 of the fibrous layer, but showed no staining in the inner 1/2 to 2/3 of the fibrous layers. Conclusion: The present lectin histochemical study provided a useful information to assess the characterization and distribution of various glycoconjugates in each constituent of human pulmonary tubercles. The results demonstrate structural differences in the glycoconjugate composition of various components of the tubercles and reveal changes in glycosylation in the components during soft tubercle formation. This study provides a new data useful for the studies on the pathogenesis and pathology of human pulmonary tubercles.