• Title/Summary/Keyword: Hypersecretion

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Morphological remodeling in mouse vagina due to hormonal hypersecretion

  • Oh, Min-Gee;Kim, Sang-Hwan
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.1
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    • pp.42-47
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    • 2022
  • This study aimed to determine whether hormonal hypersecretion could cause morphological problems in the mouse vagina and affect the ovaries and nearby extra uterine organs. All mice were synchronized to estrus before the experiment. Then human chorionic gonadotropin (hCG), progesterone, and testosterone were continuously administered for about 6 days to maintain hormone hypersecretion, and then morphological changes were analyzed, and Matrix metalloproteinases (MMPs) activity and Casp-3 expression were evaluated. As a result of the analysis, in the case of hCG, the morphological change did not show a significant difference from the vagina of normal estrus. In the case of progesterone, changes were observed in the mucosa zone and basal membrane, and it was confirmed that the activity of MMPs was increased in squamous epithelium cells. On the other hand, in the case of testosterone, overall changes in vaginal tissues were observed, and MMPs activity was increased to a very high level in all sections. The expression of Casp-3 was also the highest compared to other groups. Therefore, as a result of this study, it is thought that hormone hypersecretion affects the morphological changes of the vagina other than the ovaries and uterus and induces the activity of MMPs to cause morphological degeneration of tissues.

Recent Advances in the Development of Novel Drug Candidates for Regulating the Secretion of Pulmonary Mucus

  • Li, Xin;Jin, Fengri;Lee, Hyun Jae;Lee, Choong Jae
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.293-301
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    • 2020
  • Hypersecretion of pulmonary mucus is a major pathophysiological feature in allergic and inflammatory respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). Overproduction and/or oversecretion of mucus cause the airway obstruction and the colonization of pathogenic microbes. Developing a novel pharmacological agent to regulate the production and/or secretion of pulmonary mucus can be a useful strategy for the effective management of pathologic hypersecretion of mucus observed in COPD and asthma. Thus, in the present review, we tried to give an overview of the conventional pharmacotherapy for mucus-hypersecretory diseases and recent research results on searching for the novel candidate agents for controlling of pulmonary mucus hypersecretion, aiming to shed light on the potential efficacious pharmacotherapy of mucus-hypersecretory diseases.

A Case of Mucus Plug Impaction resulted in Bronchial Obstruction (광범위 기관지 폐쇄를 유발한 점액전 1례)

  • 고중화;전영명;김휘준
    • Korean Journal of Bronchoesophagology
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    • v.3 no.2
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    • pp.313-317
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    • 1997
  • Airway mucus provides the protective functions such as lubrication, barrier, disposal of trapped materials, and humidification. In the normal state, the mucus do not interfere with Bas transport and the other vital functions of lung. In diseases such as asthma, bronchitis, and cystic fibrosis, the mucus hypersecretion was physiologically developed in the response of multiple neurohumoral mechanism system. And regardless of the mechanism, many clinical sequelae result from mucus hypersecretion: atelectasis, infection, increased airway resistance, increased work of breathing, increased cough with its resultant complication. And the condensation of mucus tv mucus hypersecretion can make the mucus plug by which bronchial obstruction is developed. We have experienced a 7 Pear-old male patient with recurrent pneumonic symtom, which the bronchial obstruction was developed by the impacted mucus plug on the bronchoscopic finding. We report this case with the review of literature.

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Effects of Haengso-tang and Chwiyeon-tang on Expression of Respiratory Mucin Gene and Secretion of Airway Mucus (행소탕(杏蘇湯) 및 취연탕(取淵湯)이 호흡기 뮤신 유전자의 발현과 점액분비에 미치는 영향)

  • Kang, Won-Je;Seo, Un-Kyo
    • The Journal of Korean Medicine
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    • v.29 no.3
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    • pp.76-87
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    • 2008
  • Objectives: In this study, the author investigated whether Haengso-tang (HST) and Chwiyeon-tang (CHT) affect both in vitro mucin secretion and MUC5AC gene expression in airway epithelial cells and in vivo mucin secretion from animal model for airway mucus hypersecretion. Materials and Methods: Confluent HTSE cells (non-labeled) were chased for 30 min in the presence of HST and CHT to assess the effects of the agents on mucin secretion by enzyme-linked immunosorbent assay (ELISA), with removal of oriental herbal medicine extract from each agent-treated sample by centrifuge microfilter. Also, the effects of the agents on TNF- or EGF-induced MUC5AC gene expression in human airway epithelial cells (NCI-H292) were investigated. The author also induced hypersecretion of airway mucus by exposure of rats to SO2 for 3 weeks. Effects of orally-administered HST and CHT during 1 week on in vivo mucin secretion from tracheal goblet cells of rats were assessed using ELISA. Results: (1) HST significantly decreased in vitro mucin secretion from cultured HTSE cells. However, CHT did not affect in vitro mucin secretion from HTSE cells; (2) CHT significantly inhibited the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells. However, HST did not affect the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells; (3) CHT significantly inhibited hypersecretion of in vivo mucin. However, HST did not affect hypersecretion of in vivo mucin. Conclusion: These results suggest that CHT can not only affect the secretion of mucin but also the expression of the mucin gene and could be helpful for treating pulmonary disease caused by secretion of mucin.

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Pyunkang-hwan (Pyunkang-tang) Regulates Hypersecretion of Pulmonary Mucin from Rats with Sulfur Dioxide-Induced Bronchitis and Production and Gene Expression of MUC5AC Mucin from Human Airway Epithelial Cells

  • Seo, Hyo-Seok;Lee, Hyun Jae;Lee, Choong Jae
    • Natural Product Sciences
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    • v.20 no.3
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    • pp.196-201
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    • 2014
  • Pyunkang-hwan (Pyunkang-tang) extract (PGT) is a traditional folk medicine for controlling diverse pulmonary diseases including bronchitis, tonsiltis and pneumonitis. We investigated whether PGT significantly affects secretion, production and gene expression of airway mucin using in vivo and in vitro experimental models reflecting the hypersecretion and/or hyperproduction of mucus observed in inflammatory pulmonary diseases. For in vivo experiment, effect of PGT was checked on hypersecretion of pulmonary mucin in sulfur dioxide-induced bronchitis in rats. For in vitro experiment, confluent NCI-H292 cells were pretreated with PGT for 30 min and then stimulated with EGF (epidermal growth factor), PMA (phorbol 12-myristate 13-acetate) or TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) for 24 h. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) PGT inhibited the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-${\alpha}$ from NCI-H292 cells, respectively; (2) PGT also inhibited the production of MUC5AC mucin protein induced by the same inducers from NCI-H292 cells, respectively; (3) PGT inhibited secretion of mucin in sulfur dioxide-induced bronchitis rat model. This result suggests that PGT can regulate secretion, production and gene expression of airway mucin.

Effects of Seonbangpaedoktang on secretion of airway mucin and contractility of tracheal smooth muscle (선방패독탕(仙方敗毒湯)이 호흡기 뮤신 분비 및 기관 평활근 긴장도에 미치는 영향)

  • Han, Jae-Kyung;Kim, Yun-Hee;Song, Hyun-Jee
    • The Journal of Pediatrics of Korean Medicine
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    • v.21 no.1
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    • pp.139-154
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    • 2007
  • Objectives : The author intended to investigate Seonbangpaedoktang (SBPT) significantly affect in vivo and in vitro mucin secretion from airway epithelial cells. Methods : In vivo experiment, the author induced hypersecretion of airway mucin, hyperplasia of tracheal goblet cells and the increase in intraepithelial mucosubstances. Effects of orally-administered SBPT during 1 week on in vivo mucin secretion and hyperplasia of tracheal goblet cells were assessed. For in vitro experiment, confluent hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled and chased in the presence of SBPT to assess the effect of the agent on 3H-mucin secretion. Total elution profiles of control spent media and treatment sample through Sepharose CL-4B column were analysed. Possible cytotoxicity of the agent was assessed by measuring LDH release. Also, the effect of SBPT on contractility of isolated tracheal smooth muscle was investigated. Results : SBPT inhibited hypersecretion of in vivo mucin and inhibited the increase of number of goblet cells ; SBPT did not affect in vitro mucin secretion and the secretion of the other releasable glycoproteins with less molecular weight than mucin from cultured HTSE cells, without significant effect on LDH release; SBPT did not affect Ach-induced contraction of isolated tracheal smooth muscle. Conclusions : SBPT can inihibit hypersecretion of in vivo mucin and the author suggest that the effect SBPT with their components should investigate further.

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Effects of Several Oriental Medicines on Protein Kinase C Activator-Induced Production and Gene Expression of Airway Mucin and Animal Model for Airway Mucus Hypersecretion (단백질인산화효소 C 활성화제로 유도된 기도 뮤신 생성 및 유전자 발현과 점액 과분비 모델동물에 대한 수종(數種) 방제의 영향)

  • Lim, Do-Hee;Park, Yang-Chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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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.

Effects of Gagam-jeonggitang, Gami-hwajeongjeon and Gami-tonggyutang on secretion of airway mucus In Vitro and In Vivo (가감정기탕(加減正氣湯), 가미화정전(加味和正煎), 가미통규탕(加味通竅湯)이 기도점액 분비에 미치는 영향)

  • Han, Jae-Kyung;Kim, Yun-Hee;Chae, Ho-Youn
    • The Journal of Pediatrics of Korean Medicine
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    • v.21 no.1
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    • pp.117-137
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    • 2007
  • Objectives : In the present study, the author intended to investigate Gagam-jeonggitang(GJT), Gami-hwajeongjeon(GHJ) and Gami-tonggyutang(GTT) significantly affect in vivo and in vitro mucin secretion from airway epithelial cells. Methods : In vivo experiment, the author induced hypersecretion of airway mucin, hyperplasia of tracheal goblet cells and the increase in intraepithelial mucosubstances by exposing rats to SO2 during 3 weeks. Effects of orally-administered GJT, GHJ and GTT during 1 week on in vivo mucin secretion and hyperplasia of tracheal goblet cells were assesed using ELISA and staining goblet cells with alcian blue. For in vitro experiment, confluent HTSE cells were metabolically radiolabeled with 3H-glucosamine for 24 hrs and chased for 30 min in the presence of each agent to assess the effects of each agent on 3H-mucin secretion. Possible cytotoxicities of each agent were assessed by measuring lactate dehydrogenase release. Also, the effects of each agent on contractility of isolated tracheal smooth muscle and effects of each agent on MUC5AC gene expression in cultured HTSE cells were investigated. Results : GJT, GHJ and GTI inhibited hypersecretion of in vivo mucin: GJT and GHJ inhibited the increase of number of goblet cells. However, GTT did not affect the increase of number of goblet cells; GJT and GTT significantly increased mucin secretion from cultured HTSE cells, without significant cytotoxicity. GHJ increased mucin secretion and showed mild cytotoxicity at the highest concentration: GJT, GHJ and GTT chiefly affected the 'mucin' secretion; GJT, GHJ and GTT did not affect Ach-induced contraction of isolated tracheal smooth muscle; GTT did not significantly affect the expression levels of MUC5AC gene. However, GJT significantly. inhibit the expression levels of MUC5AC gene and GHJ significantly increased the expression levels of MUC5AC gene. These results suggest that GJT, GHJ and GTI can increase mucin secretion during short-term treatment(in vitro), whereas it can inihibit hypersecretion of mucin during long-term treatment(in vivo) and GJT and GHJ can not only affect the secretion of mucin but also affect the expression of mucin gene. Conclusions : The author suggests that the effects GJT, GHJ and GTT with their components should be further investigated and it is valuable to find, from oriental medical prescriptions, novel agents which might regulate hypersecretion of mucin from airway epithelial cells.

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The Role of Neutrophils and Epidermal Growth Factor Receptors in Lipopolysaccharide-Induced Mucus Hypersecretion (리포다당질 (lipopolysaccharide)에 의한 기관지 점액 생성 기전에서 호중구와 상피세포 성장인자 수용체 (epidermal growth factor receptor)의 역할)

  • Bak, Sang Myeon;Park, Soo Yeon;Hur, Gyu Young;Lee, Seung Heon;Kim, Je Hyeong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.1
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    • pp.80-90
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    • 2003
  • Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.