• IMMUNE NETWORK
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• v.19 no.1
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• pp.5.1-5.12
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• 2019

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.440-450
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• 2024

Bronchiectasis is a chronic respiratory disease characterized by abnormal dilation of the bronchi that causes cough, sputum, and recurrent infections. As it may be associated with various respiratory or systemic diseases, a critical aspect of managing bronchiectasis is to identify the underlying cause. Immunodeficiency is a rare but important cause of bronchiectasis, and its treatability is a significant trait for bronchiectasis management. While primary immunodeficiencies in bronchiectasis are well recognized, secondary immunodeficiencies remain under-reported and under-researched. Secondary immunodeficiencies may result from various diseases and conditions, such as hematologic malignancies, human immunodeficiency virus infection, renal transplantation, or the use of immunosuppressive drugs, and may contribute to the occurrence of bronchiectasis. Recurrent pulmonary and/or extrapulmonary infections in bronchiectasis may indicate the presence of secondary immunodeficiency in patients with these underlying conditions. For treatment, examining the underlying condition, managing bronchiectasis adequately, and prophylactic antibiotics (e.g., macrolide) and/or supplementary immunoglobulin G therapy may provide potential benefits. Considering the projected increase in the prevalence of secondary immunodeficiencies and bronchiectasis, future guidelines and research on the diagnosis and optimized treatment are needed.

• Parasites, Hosts and Diseases
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• v.54 no.3
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• pp.281-289
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• 2016

Clonorchis sinensis is a Group-I bio-carcinogen, associated with cholangiocarcinoma (CCA). The hamster is the only experimental model of C. sinensis-mediated CCA, but we oblige another animal model. The present study intended to develop a C. sinensis (Cs) mediated CCA model using C3H/He mice, co-stimulated with N-nitrosodimethylamine (NDMA) and dicyclanil (DC). The mice were divided into 8 groups with different combinations of Cs, NDMA, and DC. Six months later the mice were sacrificed and subjected to gross and histopathological examination. The body weights were significantly reduced among the groups treated with 2 or more agents (eg. Cs+NDMA, Cs+DC, NDMA+DC, and Cs+NDMA+DC). In contrast, liver weight percentages to body weight were increased in above groups by 4.1% to 4.7%. A Change of the spleen weight was observed only in Cs+NDMA group. Though C. sinensis infection is evident from hyperplastic changes, only 1 worm was recovered. Two mice, 1 from Cs and the other from Cs+DC group, showed mass forming lesions; 1 ($281.2mm^3$) from the Cs group was a hepatocellular adenoma and the other ($280.6mm^3$) from the Cs+DC group was a cystic mass (peliosis). Higher prevalence of gray-white nodules was observed in Cs group (42.9%) followed by Cs+NDMA+DC group (21.4%). The mice of the Cs+NDMA+DC group showed hyper-proliferation of the bile duct with fibrotic changes. No characteristic change for CCA was recognized in any of the groups. In conclusion, C3H/He mice produce no CCA but extensive fibrosis when they are challenged by Cs, NDMA, and DC together.

• Journal of the Korean Society of Radiology
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• v.81 no.1
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• pp.190-196
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• 2020

Xanthogranulomatous inflammation is a rare inflammatory reaction, characterized by lipid-laden macrophages, known as xanthomas, in histopathologic examination. Aggressive xanthogranulomatous inflammation often manifests as local infiltration but does not affect distant organs unless combined with rare systemic diseases. We report a case of focal xanthogranulomatous pyelonephritis (XGP) associated with severe xanthogranulomatous cholecystitis. Focal XGP was suspected in radiologic examination that showed a cystic lesion with an infiltrative margin, which were surgically resected and confirmed in pathologic examination. To our knowledge, this is the first report of focal xanthogranulomatous pyelonephritis associated with xanthogranulomatous cholecystitis. Moreover, we found peripheral hypointensity around the cystic lesion in the T2-weighted image, probably reflecting hemorrhage and fibrosis of the xanthogranulomatous inflammation.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.489-499
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• 1999

Background: The patient with bronchiectasis may have obstructive ventilatory impairment combined with mild restrictive ventilatory impairment due to fibrosis of surrounding lung parenchyme and pleural adhesions caused by chronic recurrent pulmonary infections. Since hyperinflation or emphysematous change can be occured in bronchiectasis, pulmonary functions such as lung volumes and diffusing capacity may also vary with associated emphysema. Methods: For the evaluation of lung volumes and diffusing capacity in bronchiectasis with respect to the anatomic types and severity of bronchiectasis, a total of 40 cases comprising 24 cases of tubular, and 16 cystic type of bronchiectasis were analyzed retrospectively. Correlation between lung functions and extent of bronchiectasis or associated emphysema detected in HRCT were also evaluated. Results: Vital capacity(VC) tended to decrease in cystic type than in tubular type. As the severity of bronchiectasis became serious, the VC were significantly reduced, whereas the total lung capacity(TLC), residual volume(RV) and its ratio to the total lung capacity(RV/TLC) had no significant difference. Lung clearance index(LCI) was significantly increased in cystic type than in tubular type, whereas the slope of phase III in single breath nitrogen curve($\triangle$N2/L) was not significantly changed regard to the type and severity of bronchiectasis. DLCO and DLCO/VA reflecting diffusing capacity were significantly decreased in cystic type and also as the severity of bronchiectasis became serious. The correlation coefficient of VC, DLCO and LCI with the extent of bronchiectasis were -0.322, -0.339 and 0.487, respectively, whereas other parameters were not significantly correlated with the extent of bronchiectasis. VC and DLCO correlated negatively with the extent of emphysema while RV, RV/TLC, LCI and $\triangle$N2/L correlated positively. Conclusion: These findings suggest that the reduction of VC and diffusing capacity or uneven distribution of inspired gas in bronchiectasis are related to both the extent of bronchiectasis and associated emphysema while increased residual volume be related to the extent of associated emphysema alone.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.4
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• pp.510-522
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• 2008

Our earlier studies showed that estrogen was involved in the regulation of fluid reabsorption in adult mouse efferent ductules (ED), through estrogen receptor (ER) ${\alpha}$ and $ER{\beta}$ by modulating gene expression of epithelial genes involved in ion homeostasis. However, little is known about the importance of $ER{\alpha}$ in the ED during postnatal development. Based on previous findings, we hypothesized that there should be a difference in the expression of epithelial ion transporters and anion producers in the ED of postnatal wild type (WT) and estrogen receptor ${\alpha}$ knockout (${\alpha}ERKO$) mice. Using absolute, comparative and semi-quantitative RT-PCR along with immunohistochemistry, we looked at expression levels of several genes in the ED across postnatal development. The presence of estrogen in the testicular fluid was indirectly ascertained by immunohistochemical detection of the P450 aromatase in the testis. There was no immunohistochemically detectable difference in the expression of P450 aromatase in the testes and ER${\beta}$ in the ED of WT and ${\alpha}$ERKO mice. ER${\alpha}$ was only detected in the ED of WT mice. The absence of ER${\alpha}$ in the ED of postnatally developing mice resulted in differential expression of mRNAs and/or proteins for carbonic anhydrase II, $Na^+/H^+$ exchanger 3, down-regulated in adenoma, cystic fibrosis transmembrane regulator, and $Na^+/K^+$ ATPase ${\alpha}$. Our data indicate that the absence of ER${\alpha}$ resulted in altered expression of an epithelial ion producer and transporters during postnatal development of mice. We conclude that the presence of ER${\alpha}$is important for regulation of the ED function during the prepubertal developmental and postpubertal period.

• Development and Reproduction
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• v.17 no.3
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• pp.289-297
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• 2013

Bisphenol A (BPA) is an estrogenic endocrine disrupter. However, depending on a way of treatment, the harmful effects of BPA have not been confirmed. Also, trans-generational effects of BPA on male reproduction are still controversial. Because the reabsorption of testicular fluid in the efferent ductules (ED) and initial segment (IS) is important for sperm maturation, the present study was designed to determine trans-generational effect of BPA administrated orally on expression of water transport-related molecules in the mouse ED and IS. Ethanol-dissolved BPA was diluted in water to be 100 ng (low), $10{\mu}g$ (medium), and $1mg/m{\ell}$ water (high). BPA-containing water was provided for two generations. Expression of ion transporters and water channels in the ED and IS were measured by relative real-time PCR analysis. In the ED, BPA treatment caused expressional increases of carbonic anhydrase II, cystic fibrosis transmembrane regulator, $Na^+/K^+$ ATPase ${\alpha}1$ subunit, and aquaporin (AQP) 1. No change of $Na^+/H^+$ exchange (NHE) 3 expression was detected. BPA treatment at medium dose resulted in an increase of AQP9 expression. In the IS, the highest expressional levels of all molecules tested were observed in medium-dose BPA treatment. Generally, high-dose BPA treatment resulted in a decrease or no change of gene expression. Fluctuation of NHE3 gene expression by BPA treatment at different concentrations was detected. These findings suggest that trans-generational exposure to BPA, even at low dose, could affect gene expression of water-transport related molecules. However, such effects of BPA would be differentially occurred in the ED and IS.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.104-107
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• 2005

Choledochal cyst is considered to be congenital anomalies of the biliary tract, characterized by varying degrees of cystic dilatation at various segments of the biliary tract. A 20-month-old girl was admitted to Eul-Ji general hospital because of abdominal distension. Physical examination revealed marked splenomegaly and hepatomegaly with nodular surface and hard consistency. Laboratory examination showed elevated transaminase level, alkaline phosphatase level and gamma glutamyltranspeptidase level without evidence of cholestasis. Diagnostic imaging study revealed choledochal cyst with Todani classification type 1. Cholecystectomy and Roux-en-Y choledochojejunostomy was performed, and wedge liver biopsy showed diffuse periportal fibrosis with cirrhotic change and ductular proliferation in the portal area. After operation, hepatosplenomegaly and abnormal laboratory examinations improved rapidly, and in 9 months, the liver and spleen became not palpable. We experienced a case of choledochal cyst complicated by liver cirrhosis on pathology in a 20 month-old girl, and removal of choledochal cyst improved clinical manifestations rapidly.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.131-138
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• 2002

Thanks to recent progress in availability of molecular and functional techniques it became possible to search for the basic molecular and cellular processes that mediate and control $HCO_3{^-}$ and fluid secretion by the pancreatic duct. The coordinated action of various transporters on the luminal and basolateral membranes of polarized epithelial cells mediates the transepithelial $HCO_3{^-}$ transport, which involves $HCO_3{^-}$ absorption in the resting state and $HCO_3{^-}$ secretion in the stimulated state. The overall process of HCO3 secretion can be divided into two steps. First, $HCO_3{^-}$ in the blood enters the ductal epithelial cells across the basolateral membrane either by simple diffusion in the forms of $CO_2$ and $H_2O$ or by the action of an $Na^+-coupled$ transporter, a $Na^+-HCO_3$ cotranporter (NBC) identified as pNBC1. Subsequently, the cells secrete $HCO_3{^-}$ to the luminal space using at least two $HCO_3{^-}$ exit mechanisms at the luminal membrane. One of the critical transporters needed for all forms of $HCO_3{^-}$ secretion across the luminal membrane is the cystic fibrosis transmembrane conductance regulator (CFTR). In the resting state the pancreatic duct, and probably other $HCO_3{^-}$ secretory epithelia, absorb $HCO_3{^-}.$ Interestingly, CFTR also control this mechanism. In this review, we discuss recent progress in understanding epithelial $HCO_3{^-}$ transport, in particular the nature of the luminal transporters and their regulation by CFTR.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1539-1548
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• 2017

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that commonly causes fatal infections in cystic fibrosis and burn patients as well as in patients who are hospitalized or have impaired immune systems. P. aeruginosa infections are difficult to treat owing to the high resistance of the pathogen to conventional antibiotics. Despite several efforts, no effective prophylactic vaccines against P. aeruginosa are currently available. In this study, we investigated the activity of the CIA06 adjuvant system, which is composed of alum and de-O-acylated lipooligosaccharide, on a P. aeruginosa outer membrane protein (OMP) antigen vaccine in mice. The results indicated that CIA06 significantly increased the antigen-specific IgG titers and opsonophagocytic activity of immune sera against P. aeruginosa. In addition, the antibodies induced by the CIA06-adjuvanted vaccine exhibited higher cross-reactivity with heterologous P. aeruginosa strains. Finally, mice immunized with the CIA06-adjuvanted vaccine were effectively protected from lethal P. aeruginosa challenge. Based on these data, we suggest that the CIA06 adjuvant system might be used to promote the immunogenicity and protective efficacy of the P. aeruginosa OMP vaccine.