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.
Objectives : This is the experimental paper to study the curative and preventive effects of Dansambohyultang, Methods : Oriental herb medicine for gastro-intestinal disease caused by stress, on the rats put under the stress through starvation, heating and immoblization, the author used four different group; the normal group, which was not put under stress and well fed, and the control group, to which the drug was not administered and put under the stress through starvation, heating and immoblization, the Sample I, to which the drug was administered before they were put under stress, the Sample lI, to which the drug was administered after they were put under stress. Results : When a Masson's trichrome stain method was applied to the control group, a small size of ulcer was found in the fundus and the pylorus, and atrophy was observed in the neck region of mucous membrane. When the drug was administered to the Sample I and the Sample II, the former recovered from the ulcer and atrophy to almost normal and showed better results than the latter. When a Masson's trichrome stain method was applied to the control group, atrophy of mucous membrane was found all over the intestines. When the drug was administered to the Sample I and the Sample ll, the curative and recovered effects was seen in both, but the former showed better results than the latter. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cells in the small intestines showed the most significant decrease in the control group. In the Sample I, the number of the cells in the duodenum, the jejunum and the ileum returned to an almost normal level. In the Sample II, a slight increase was observed only in the ileum. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cell in the large intestines showed a significant decreased in the control group. Both the Sample I and the Sample II showed an increase in the number of goblet cells in comparison with the control group. When a serotonin-immunoreaction test was applied, the control group showed a general decrease in the number of gastro-entero-endocrine cells, The Sample I showed the effect in all over gastro.intestinal tract as compared with control group and the Sample II showed the effect in all over gastro-intestinal tract except the duodenum and the former showed better results than the latter. Conclusion : According to the above results, the regions which are most sensitive to stress were observed to the ileum and the colon. It was concluded that Dansambohyultang has a remedical value particularly on the abnormalities caused by stress in all over gastro-intestinal tract and it was found to be more effective in the Sample I than in the Sample ll. Judging from the fact that the Sample I showed better results than the Sample ll, Dansambohyultang can be said to have a preventive effect more than a curative effect on gastro-intestinal tract disease.
The last two decades witnessed significant advances in the efforts of immune-parasitologists to elucidate the nature and role of the host mucosal defence mechanisms against intestinal nematode parasites. Aided by recent advances in basic immunology and biotechnology with the concomitant development of well defined laboratory models of infection, immunoparasitologists have more precisely analyzed and defined the different immune effector mechanisms during the infection; resulting in great improvement in our current knowledge and understanding of protective immunity against gastrointestinal (GI) nematode parasites. Much of this current understanding comes from experimental studies in laboratory rodents, which have been used as models of livestock and human GI nematode infections. These rodent studies, which have concentrated on Heligmosomoides polygyrus, Nippostrongylus brasiliensis, Strongyloides ratti/5. venezuelensis. Trichinella spiralis and trichuris muris infections in mice and rats, have helped in defining the types of T cell responses that regulate effector mechanisms and the effector mechanisms responsible for worm expulsion. In addition, these studies bear indications that traditionally accepted mechanisms of resistance such as eosinophilia and IgE responses may not play as important roles in protection as were previously conceived. In this review, we shall, from these rodent studies, attempt an overview of the mucosal and other effector responses against intestinal nematode parasites beginning with the indices of immune protection as a model of the protective immune responses that may occur in animals and man.
The present studies were designed to determine the feasibility of using the rat tracheal epithelium as models for induction of aging. The ultrastructural and cytochemical changes of tracheal epithelium were investigated in rats at ages of five, twelve and twenty four months. Some major changes in the tracheal epithelium with advancing age were observed by electron microscopy. The results were summarized as fellow: 1. With the advance of age, lysosome, vacuole and multivesicular bodies were increased in number and numerous myelinoid bodies were observed in cytoplasm of ciliated cells. 2. In goblet cell, serous cell and brush cell lysosome and myelinoid bodies were increased in number with the advance of age, and an myelinoid bodies was often found within the secretory granule. 3. Cytochemical studies showed that acid phosphatase activities was observed in multivesicular bodies and lysosome, strong activities with the advance of age. And alkaline phosphatase activity are observed in microvilli, granule and lateral membrane of secretory granule cells, and strong activities with age. Consequently suggest that with the advance of age, tracheal epithelium show ultrastructural and cytochemical alteration of some kind of cell organelles in all kind of cell.
Mucinase complex from V. parahaemolyticus ATCC 17802 was purified 6-fold with 0.4% yield by two sequential steps of Q-Sepharose and Superdex 200HR column chromatographies. Partially purified mucinase complex showed at least 8 times higher mucin-degrading activity than the culture filtrates. The mucinase complex also showed gelatin-and-casein-hydrolyzing activities, which demonstrates that the protein is a complex compound containing several proteases. The optimum pH and temperature of partially purified mucinase complex for mucin degradation was 8.0 and $35^{\circ}C$, respectively. The partially purified mucinase complex showed high cytotoxic activity on vero cells when examined by MTT assay and microscopic observations. Cytotoxicity was significantly increased in proportion to the concentration of the mucinase complex. Mouse experiments revealed that the jejunum, ileum. and large intestinal tissues were damaged by the injection of the mucinase complex. In particular, the reduction of the goblet cells in the large intestine was remarkable. Collectively, these data suggest that the mucinase complex partially purified from V. parahaemolyticus ATCC 17802 contributes to the adhesion and invasion of V. parahaemolyticus into the host intestinal tract.
Recent studies have shown that probiotics have health-promoting effects, particularly intestinal immune modulation. In this study, we focused on the immunomodulatory properties of Latilactobacillus curvatus BYB3, formerly called Lactobacillus curvatus, isolated from kimchi. In a mouse model of 14-day dextran sulfate sodium (DSS)-induced colitis, treatment with L. curvatus BYB3 significantly decreased the disease activity index, colon length, and weight loss. Moreover, histological analyses showed that L. curvatus BYB3 protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration by immune cells. To evaluate the molecular mechanisms underlying L. curvatus BYB3-driven inhibition of interleukin 6 production, possible in vivo anti-inflammatory effects of L. curvatus BYB3 were examined in the same mouse model. In addition, significantly lower levels of IL-6 and tumor necrosis factor receptor 1 upregulation were seen in the DSS+BYB3 group (compared to that in the DSS group). These results indicate that L. curvatus BYB3 exhibits health-promoting effects via immune modulation; and therefore, it can be used to treat various inflammatory diseases.
Objectives : In this study, we investigated the effects of Agastachis Herba water (AH-W) extract on compound 48/80-induced mast cell degranulation and histamine release in human mast cells and also anti-asthmatic effect of AH-W extract on ovalbumin (OVA)-induced asthma in mice. Methods : Human mast cells, HMC-1 were treated with AH-W extract in the presence or absence of compound 48/80 (C48/80). Mast cell degranulation was observed by microscope, and the histamine release was measured in culture medium by ELISA. For preparation of asthmatic in vivo model, mice were sensitized (0, 7, and 14 days) with OVA and airway challenged (21, 23, 25, 27, and 29 days). AH-W extract at doses of 100 and 300 mg/kg/body weight was orally administered during OVA challenge once per a day. The levels of immunoglobulin (Ig) E, and Th1/Th2 cytokines, IFN-$\gamma$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed by hematoxylin and eosin (H&E) and Periodic Acid Schiff (PAS) staining. Results : The treatment of AH-W extract significantly decreased the mast cell degranulation and histamine release in C48/80-stimulated HMC-1 cells. In addition, The administration of AH-W extract at does of 100 and 300 mg/kg significantly decreased the serum levels of OVA-specific IgE compared with those of OVA control group. In H&E and PAS staining, AH-W extract inhibited OVA-induced airway inflammation, and inflammatory cells infiltration, and also histopathological damages on lung tissues such as bronchiole epithelial desquamation, goblet cells hyperplasia, and mucin releasing. Conclusions : These results indicate that AH-W extract may improve asthmatic symptoms through mast cell stabilization and inhibiting the lung inflammation in bronchial asthma.
Objective : In the present study, the author tried to investigate whether six oriental medical prescriptions named gamisingitang (SGT), gamijungtang (IJT), gamicheongpyetang (CPT), galhwengchihyosan (CHS), chwiyeontong (CYT), sigyoungcheongpyetang (SCPT) significantly affect mucin release from cultured hamster tracheal surface epithelial (HTSE) cells. Methode : Confluent HTSE cells were inetabolically radiolabeled with $^{3}H-glucosamine$ for 24 hrs and chased for 30 min in the presence of drugs aforementioned, respectively, to assess the effect of each drug on $^{3}H-mucin$ release. Possible cytotoxicities of effective drugs were assessed by measuring lactate dehydrogenase(LDH) release. Additionally, total elution profiles of control spent media and treatment sample (CPT, CHS, SCPT and CYT) through Sepharose CL-4B column were analysed and effect of CPT, CHS and CYT on MUC5AC mRNA expression in cultured HTSE cells were invsetigated. Results : (1) SGT and IJT did not affect mucin release without cytotoxicity; (2) CPT, SCPT and CHS significantly stimulated mucin release from cultured HTSE cells, with significant cytotoxicity; (4) CPT, CHS, SCPT and CYT chiefly affected the 'mucin' release and did not affect significantly the release of the releasable glycoproteins with less molecular weight than mucin. This result suggests that the four herbal prescriptions specifically affect the release of mucin ; (5) CTP and CHS did not significantly affect the expression levels of MUC 5AC mRNA, however, CYT significantly inhibit the expression levels of MUC 5AC mRNA. Conclusion : CYT can decrease the synthesis of mucin at gene level in cultured HTSE cells.
Objectives : This study was done to investigate whether two oriental prescriptions, saganmahwang-tang (SMT) and prescription C (P-C) significantly affect mucin release from cultured hamster tracheal surface epithelial (HTSE) cells. Methods : Cofluent HTSE cells were metabolically radiolabeled with 3H-glucosamine for 24 hrs and chased for 30 min in the presence of SMT or P-C to assess the effect of each agent on 3H-mucin release. Possible cytotoxicities of each agent were assessed by measuring lactate dehydrogenase (LDH) release. Also, the effects of SMT and P-C on contractility of isolated tracheal smooth muscle were investigated. Results : SMT significantly inhibited mucin release from cultured HTSE cells, without cytotoxicity. P-C significantly increased mucin release from cultured HTSE cells, with significant cytotoxicity. SMT inhibited Ach-induced contraction of isolated tracheal smooth muscle. P-C did not affect Ach-induced contraction of isolated tracheal smooth muscle. Conclusion : Results su99est that SMT and P-C have regulating effects on mucin secretion from airway goblet cells. Further investigation is needed, because of the value in finding novel agents to this purpose, and these oriental medical prescription have potential for such a role.
Objectives In this study, effect of Geumsuyukgunjeon (GYJ) on the increase in airway epithelial mucosubstances of rats with acute bronchitis and EGF-induced MUC5AC mucin production from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered GYJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of GYJ was assessed by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering GYJ orally. Effect of GYJ on EGF-induced MUC5AC mucin production from human airway epithelial cells (A549) was investigated. Confluent A549 cells were pretreated for 30 min in the presence of GYJ and treated with EGF (25 ng/ml) for 24 hrs, to assess the effect of GYJ on EGF-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA). Results (1) GYJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) GYJ did not show kidney and liver toxicities and did not affect body weight gain of rats during experiment. (3) GYJ significantly inhibited EGF-induced MUC5AC mucin production from A549 cells. Conclusions The result from the present study suggests that GYJ might control both the mucus hypersecretion in vivo and do not show in vivo toxicity to liver and kidney functions after oral administration and the production of pulmonary mucin.
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