• Parasites, Hosts and Diseases
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• 제51권5호
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• pp.589-594
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• 2013

In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.

• Parasites, Hosts and Diseases
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• 제52권3호
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• pp.273-280
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• 2014

The changing patterns of goblet cell hyperplasia, intestinal epithelial cell turnover, and intestinal motility were studied in ICR and C57BL/6 mice infected with Gymnophalloides seoi (Digenea: Gymnophallidae). Whereas ICR mice retained G. seoi worms until day 7 post-infection (PI), C57BL/6 mice showed a rapid worm expulsion within day 3 PI. Immunosuppression with Depo-Medrol significantly delayed the worm expulsion in C57BL/6 mice. Goblet cell counts were increased in both strains of mice, peaking at day 1 PI in C57BL/6 mice and slowly increasing until day 7 PI in ICR mice. In C57BL/6 mice infected with G. seoi, newly proliferating intestinal epithelial cells were remarkably increased in the crypt, and the increase was the highest at day 1 PI. However, in ICR mice, newly proliferating intestinal epithelial cells increased slowly from day 1 to day 7 PI. Intestinal motility was increased in G. seoi-infected mice, and its chronological pattern was highly correlated with the worm load in both strains of mice. Meanwhile, immunosuppression of C57BL/6 mice abrogated the goblet cell proliferation, reduced the epithelial cell proliferation, and suppressed the intestinal motility. Goblet cell hyperplasia, increased intestinal epithelial cell turnover, and increased intestinal motility should be important mucosal defense mechanisms in G. seoi-infected C57BL/6 mice.

• Tuberculosis and Respiratory Diseases
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• 제54권1호
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• pp.80-90
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• 2003

배경 : 본 연구에서는 세균성 리포다당질(lipopolysac-charide, LPS)로 인한 호중구성 염증이 EGFR 시스템을 통해서 배상 세포의 이형성 및 점액의 과다 분비를 유발할 것이라는 가설 하에, LPS와 MMPs 억제제(matrix metalloproteinase inhibitor, MMPI)를 투여한 후 EGFR 및 MMP-9의 발현을 연구하고자 하였다. 방법 : Pathogen-free Sprague-Dawley 를, 다양한 농도의 LPS를 투여한 군과 투여하지 않은 대조군으로 나누어 기도의 조직학적인 변화를 날짜 별로 관찰하였고, MMPI(CMT-3)를 LPS 투여 3일 전부터 매일 구강을 통해 섭식시켰다. 호중구의 침윤은 다섯 개의 고배율 시야에서 관찰된 호중구의 수로 정량화하여 비교하였고, mucus glycoconjugate에 대한 AB/PAS 염색 및 MUC5AC, EGFR, MMP-9에 대한 면역조직화학 염색 (immunohistochemical stain)을 시행하였다 결과 : LPS를 투여한 경우 기도 상피의 AB/PAS 및 MUC5AC의 염색 정도는 시간 및 용량 의존적으로 증가하였고, MMPI를 치료할 경우에 LPS로 인한 배상세포의 과형성이 유의하게 감소하였다. LPS를 주입할 경우 호중구의 침윤이 증가하였고 기도 상피에서 EGFR의 발현을 증가시켰다. MMPI로 치료할 경우 LPS로 인한 호중구의 침윤 및 EGFR의 발현 그리고 배상세포의 과형성이 현저하게 감소되었다. 결론 : Matrix metalloproteinase는 호중구성 염증 및 EGFR에 의해 발생하는 LPS에 의한 배상 세포의 과형성 및 점액 과다분비의 기전에 있어서 밀접하게 관련되고, 따라서 점액 과다분비를 특징으로 하는 세균 감염으로 인한 기도 질환의 치료에 있어서 MMPI가 잠재적인 임상적 효과가 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제49권1호
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• pp.37-48
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• 2000

연구배경 : 기관지 천식등과 같은 만성 기도질환의 병태생리는 점액의 과분비, 배상세포의 과형성, 평활근의 비후와 호산구등의 염증세포의 침윤등으로 설명되고 있다. 배상세포의 증식에 대한 생화학적 기전은 이러한 양상을 만드는데 필요한 시간이 길고, 기도염증과 연관된 매우 복잡함 때문에 아직 잘 알려지지 않고 있다. 이에 본 저자들은 배상세포증식과 기도염증의 상관성을 알고자 그 첫 단계로 백서의 기관을 통한 $TiO_2$의 주입으로 단시간 내에 형성되는 배상세포증식의 동물 모형을 만들어 기도내 주로 어느 부위에서 배상세포의 과형성이 나타나는지 관찰하고 염증세포의 침윤 여부 및 dexamethasone 이 과형성된 배상세포 및 침윤된 염증세포에 대해 영향을 평가해 보고자 하였다. 방법 : 8주된 21마리의 수컷 Sprague-Dawley를 세 군으로 나누어서 첫 번째 군(group 1) 은 endotoxin-free water를 기관내 주입하고 두 번째 군(group 2)은 $TiO_2$를 주입을 하고 세 번째 군(group 3)은 $TiO_2$를 주입하고 dexamethasone을 $TiO_2$ 투여전날부터 희생전날까지 투여하였다. 흰쥐를 희생시켜 기관, 기관지와 폐 부위를 각각 절제하여 paraffin bloc을 만든 후 $4{\mu}m$의 section을 하여 PAS 염색한 후 각 부위에서의 상피세포에 대한 배상세포의 비를 구하여 각 군별로 비교하였고, Luna 염색으로 호산구의 침윤을 비교하였다. 결과 : 1. 기관에서의 배상세포의 비의 평균은 1군에서는 4.09$\pm$8.28%, 2군은 10.19$\pm$11.33%로 $TiO_2$를 주입한 2군에서 배상세포의 과형성을 관찰할 수 있었다 (P<0.01). 2. 주 기관지에서의 배상세포의 비의 평균은 1군에서 3.61$\pm$4.84%, 2군에서는 34.09$\pm$23.91%로 $TiO_2$를 주입한 2군에서 배상세포의 과형성을 관찰 할 수 있었다(P<0.01). 3. 세기관지 부위에서의 배상세포의 양성 incidence와 severity (R$\times$S)로 표시를 하였으며 이는 각각 1 군은 0, 2군은 0.3 이었다. 4. 침윤된 호산구는 1군(1.99$\pm$3.84%)에서보다 2군 (21.43$\pm$23.85%)에서 유의하게 증가되었다(p<0.05). 5. 1군, 2군, 3군의 주기관지내에서 배상세포의 과형성과 호산구 침윤간에는 의미있는 상관관계를 보였다(p=0.001). 6. dexamethasone이 배상세포의 과형성과 호산구의 침윤을 억제함을 관찰하였다. 결론 : 백서에서 $TiO_2$로 처치시 기도에서 배상세포의 과형성이 5일내에 주로 주 기관지에서 발생하였으며 호산구 침윤이 동반하는 배상세포 증식의 동물 모형이 만들어졌다. 배상세포의 과형성은 염증과 동반되며 dexamethasone 투여시 억제되므로, 배상세포의 증식기전 에서 기도내 염증과정이 주요한 역할을 하는 것으로 생각된다. 향 후 이러한 동물 모형은 배상세포 증식의 기전을 이해하는데 유용한 도구가 될 것으로 사료된다.

• 동의생리병리학회지
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• 제22권6호
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• pp.1500-1508
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• 2008

The author investigated whether Chwiyeon-tang(PC), Haengso-tang(PH), Jawanchihyo-san(PJ) and Gamisocheongryong-tang(PS) significantly affect both PMA-induced mucin production and MUC5AC gene expression in airway epithelial cells and sulfur-dioxide-induced airway goblet cell hyperplasia and mucus hypersecretion animal model using rat. Possible cytotoxicity of each herbal medicine was assessed by measuring the survival and proliferation rate of NCI-H292 cells. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PC, PH, PJ and PS, respectively, and treated with PMA(10 $ng/m{\ell}$), to assess the effect of each herbal medicine on PMA-induced mucin production by enzyme-linked immunosorbent assay(ELISA). Effects of each herbal medicine on PMA-induced MUC5AC gene expression from the same cells were investigated. Also, hypersecretion of airway mucus and goblet cell hyperplasia were induced by exposure of rats to $SO_2$ during 3 weeks. Effects of orally-administered PC, PH, PJ and PS during 1 week on intraepithelial mucosubstances and hyperplasia of goblet cells were examined using histological analysis after staining the epithelial tissue with PAS-alcian blue. (1) PC, PJ, PS and PH did not show significant effects on the survival and proliferation of NCI-H292 cells ; (2) PC, PJ and PS significantly decreased PMA-induced mucin production from NCI-H292 cells ; (3) PC, PJ and PS significantly inhibit the expression levels of PMA-induced MUC5AC gene in NCI-H292 cells ; (4) Among PC, PJ, PS and PH, only PS decreased $SO_2$-induced hyperplasia of airway goblet cells and intraepithelial mucosubstances. This result suggests that PC, PJ and PS can not only affect the production of mucin but also affect the expression of mucin gene and this can explain, at least in part, the traditional use of PC, PJ and PS for controlling airway diseases showing hypersecretion of mucus in oriental medicine.

• Parasites, Hosts and Diseases
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• 제39권1호
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• pp.31-41
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• 2001

The intestinal histopathology and in situ postures of Gymnophalloides seoi (Digenea: Gymnophallidae) were studied using C3H/HeN and C57BL/6 mice as experimental hosts; the effects of immunosuppression were also observed. The metacercariae isolated from naturally infected oysters, 300 or 1,000 in number, were infected orally to each mouse, and the mice were killed at days 3-21 post-infection (PI). In immunocompetent (IC) mice, only a small number of flukes were found in the mucosa of the duodenum and jejunum during days 3-7 PI, with their large oral suckers pinching and sucking the root of villi. The intestinal mucosa showed mild villous atrophy crypt hyperplasia, and inflammations in the villous stroma and crypt, with remarkable goblet cell hyperplasia. These mucosal changes were almost restored after days 14-21 PI. In immunosuppressed (IS) mice. displacement as well as complete loss of villi adjacent to the flukes was frequently encountered, otherwise the histopathology was generally mild, with minimal goblet cell hyperplasia. In these mice, numerous flukes were found, and it seemed that they were actively moving and rotating in situ. Several flukes were found to have invaded into the submucosa, almost facing the serosa. These results indicate that in IC mice the intestinal histopathology caused by G. seoi is generally mild, and the flukes do not penetrate beyond the mucosa, however, in IS mice. the flukes can cause severe destruction of neighboring villi. and some of them invade into the submucosa.

• 동의생리병리학회지
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• 제26권1호
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• pp.40-46
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• 2012

Cigarette smoking is known to be associated with various chronic pulmonary and cardiovascular diseases ranging from inflammation to cancer. Not only first-hand smoke but also second-hand smoke is suggested to be a factor of health risk. This study was to investigate whether Platycodi Radix extract administration would alter oxidative stress in lung leading to protection of cigarette smoke-induced lung damage. Sprague-Dawley rats were randomly divided into 3 groups; Intact, Smoke+PR and Smoke+Vehicle. In Smoke+PR and Smoke+Vehicle group, the exposure to cigarette smoke was performed for 15 min/day for 4 weeks in ventilated smoking chamber. The Platycodi Radix extract and saline were orally administrated to Smoke+PR and Smoke+Vehicle group each. The rats of Intact group were just kept in ventilated chamber without cigarette smoke. After the experiment for 4 weeks, the lung tissues were collected for histological observation and immunohistochemistry. In Results, airspace enlargement and goblet cell hyperplasia were observed after 4 weeks' exposure to cigarette smoke. Whereas, the oral administration of Platycodi Radix extract for 4 weeks reduced airspace enlargement and goblet cell hyperplasia. Moreover, the alterations of BAX/Bcl-2 proteins in lung tissues were observed. These results suggest that Platycodi Radix extract ameliorates lung damage in cigarette smoke-exposed rats and has protective effects on second-hand smoke injury.

• Molecules and Cells
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• 제45권6호
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• pp.353-361
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• 2022

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

• Molecules and Cells
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• 제22권1호
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• pp.104-112
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• 2006

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-${\kappa}B$ by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-${\kappa}B$ increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-${\kappa}B$ pathway.

• Nutrition Research and Practice
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• 제11권6호
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• pp.461-469
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• 2017

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed $2{\mu}g$/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 ${\mu}g$/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ${\geq}50$ mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.