• The Korean Journal of Physiology and Pharmacology
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• 제9권6호
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• pp.323-326
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• 2005

In the present study, we investigated whether ambroxol, S-carboxymethyl-L-cysteine, dextromethorphan and noscapine affect mucin release from airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled and chased for 30 min in the presence of varying concentrations of the above agents to assess the effects on $^3H$-mucin release. Noscapine stimulated mucin release during 30 min of treatment period in a dose-dependent manner. However, ambroxol, S-carboxymethyl-L-cysteine and dextromethorphan showed no significant effect on mucin release during 30 min of treatment period. We conclude that noscapine can affect mucin release by acting on airway mucin-secreting cells.

• Natural Product Sciences
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• 제20권3호
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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.

• Tuberculosis and Respiratory Diseases
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• 제41권2호
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• pp.73-86
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• 1994

In addition to classic cholinergic and adrenergic pathways, the existence of a third division of autonomic control in the human airways has been proved. It is called a nonadrenergic noncholinergic(NANC) nervous system, and difficult to study in the absence of specific blockers. Neuropeptides are certainly suggested to be transmitters of this NANC nervous system. It is very frustrating to understand the pathophysiologic role of these peptides in the absence of any specific antagonists. However, further studies of neuropeptides might eventually lead to novel forms of treatment for bronchial asthma. Another study of the interaction between different components of the autonomic nervous system, either in ganglionic neurotransmission or by presynaptic modulation of neurotransmitters at the end-organ will elute neural control in airway disease, particularly in asthma. Studies of how autonomic control may be disordered in airway disease should lead to improvements in clinical management. Epithelial damage due to airway inflammation in asthma may induce bronchial hyperresponsiveness. Axon reflex mechanism is one of possible mechanisms in bronchial hyperresponsiveness. Epithelial damage may expose sensory nerve terminals and C-fiber nrve endings are stimulated by inflammatory mediators. Bi-directional communication between the nerves and mast cells may have important roles in allergic process. The psychological factors and conditioning of allergic reactions is suggested that mast cell activation might be partly regulated by the central nervous system via the peripheral nerves. Studies in animal models, in huamn airways in vitro and in patients with airway disease will uncover the interaction between allergic disease processes and psychologic factors or neural mechainsms.

• 대한한방내과학회지
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• 제26권1호
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• pp.199-212
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• 2005

Objective : Airway inflammation is now regarded as a defining feature of asthma. The importance of eosinophits in the airway inflammation of asthma patients is widely recognized, and eosinophils mobilization in the respiratory epithelium is activated by chemoattractants and cytokines. This study was designed to examine the extent of the ability of Moutan Cortex Radicis to inhibit eosinophil chemotaxis of pulmonary epithelium after allergic stimulation. Material and Methods : Water extracts of Moutan Cortex Radicis and pulmonary epithelial cell lines A549(human type II-like epithelial cells) and human eosinophils were used. Cytotoxic effects of Moutan Cortex Radicis were estimated via MTS assay, and the effects of Moutan Cortex Radicis on chemokines from prestimulated A549 cells were estimated by sandwich ELISA and RT-PCR. Chemotaxis assay on prestimulated eosinophils treated with Moutan Cortex Radicis. was conducted Result : In this study we demonstrated that $TNF-{\alpha}$ and IL-4, $IL-1{\beta}$ induced the accumulation of chemokines' mRNA in the pulmonary epithelial cell lines A549 in a dose-dependent manner. Chemokines of eotaxin, ICAM-1, YCAM-1, IL-8, IL-16 were inhibited by Moutan Cortex Radicis in a dose dependent manner, but RANTES showed no inhibition due to Moutan Cortex Radicis. Eosinophil migration was inhibited at high concentrations of Moutan Cortex Radicis. Conculusion : These findings are indicative of supression of chemokines accomplished by Moutan Cortex Radicis treatment, demonstrating the potential therapeutic value of Moutan Cortex Radicis for treating diseases such as asthma.

• Tuberculosis and Respiratory Diseases
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• 제42권4호
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• pp.447-454
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• 1995

Cytokine release from alveolar macrophages and subsequent interaction of these cytokines with the bronchial epithelium can induce epithelial cells to release inflammatory mediators. Nitric oxide(NO), a highly reactive gas formed from arginine by nitric oxide synthase(NOS), is known to be involved in inflammation and edema formation, and the inducible form of NOS(iNOS) can be increased by cytokines. In this context, we hypothesized that lung epithelial cells could be stimulated by cytokines released by alveolar macrophages to express iNOS. To test this hypothesis, the murine lung epithelial cell line, LA-4, or the human lung epithelial cell line, A549, were stimulated with culture supernatant fluids from alveolar macrophages. NO production was assessed by evaluating the culture supernatant fluids for nitrite and nitrate, the stable end products of NO. Both murine and human cell culture supernatant fluids demonstrated an increase in nitrite and nitrate which were time- and dose-dependent and attenuated by $TNF{\alpha}$ and IL-$1{\beta}$ antibodies(p<0.05, all comparisons). Consistent with these observations, cytomix a combination of $TNF{\alpha}$, IL-$1{\beta}$, and $\gamma$-interferon, stimulated the lung epithelial cell lines as well as primary cultures of human bronchial epithelial cells to increase their NO production as evidenced by an increase in nitrite and nitrate in their culture supernatant fluids, an increase in the iNOS staining by immunocytochemistry, and an increase in iNOS mRNA by Northern blottin(p<0.05, all comparisons). The cytokine effects on iNOS were all attenuated by dexamethasone. To determine if these in vitro observations are reflected in vivo, exhaled NO was measured and found to be increased in asthmatics not receiving corticosteroids. These data demonstrate that alveolar macrophage derived cytokines increase iNOS expression in lung epithelial cells and that these in vitro observations are mirrored by increased exhaled NO levels in asthmatics. Increased NO in the lung may contribute to edema formation and airway narrowing.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.431-436
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• 2020

In this study, diclofenac, a non-steroidal anti-inflammatory drug, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. The human respiratory epithelial NCI-H292 cells were pretreated with diclofenac for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of diclofenac on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Diclofenac suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest diclofenac regulates the gene expression and production of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

• 동의생리병리학회지
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• 제18권6호
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• pp.1746-1751
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• 2004

This study was done to investigate the effects of Gamichihyo-san and Gamiijung-tang on airway mucus secretion. After administer Gamichihyo-san(GCHS) and Gamiijung-tang(GIJT) extract to Golden Syrian Hamster for 8-10 weeks, we examined mucin release from cultured hamster tracheal surface epithelial(HTSE) cells. Following results were obtained; GCHG significantly stimulated mucin release from cultured HTSE cells, with minute cytotoxicity GIJT did not affect mucin release and have no cytotoxicity; GCHG and GIJT did not affect contractility of isolated tracheal smooth muscle. These results suggest that Gamichihyo-san might be usefully applied for airway mucus secretion.

• 대한한방내과학회지
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• 제29권3호
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• pp.765-777
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• 2008

Objectives : In this study, the author tried to examine whether Gamijinhae-tang and Socheongryong-tang-ga-seokgo significantly affect both PMA-induced mucin production and MUC5AC gene expression from airway epithelial cells. Materials and Methods : Confluent NCI-H292 cells were pretreated for 30 min in the presence of JHT and STS and treated with PMA (10ng/ml), to assess the effects of the agents on PMA-induced mucin production by enzyme-linked immunosorbent assay (ELISA). Also, the effects of the agents on PMA-induced MUC5AC gene expression from the same cells were investigated. Possible cytotoxicities of the agent were assessed by examining the rate of survival and proliferation of NCI-H292 cells after treatment of agents during 48 hrs. Results : (1) JHT and STS did not show significant cytotoxicity to NCI-H292 cells. (2) JHT significantly decreased PMA-induced mucin production from NCI-H292 cells. However. STS did not affect mucin production. (3) JHT significantly inhibit the expression levels of PMA-induced MUC5AC gene in NCI-H292 cells. STS slightly decreased the expression levels of PMA-induced MUC5AC gene. Conclusion : These results suggest that JHT can not only affect the production of mucin but also affect the expression of the mucin gene, and this explains the traditional use of JHT in oriental medicine. The effects of JHT and STS with their components should be further investigated using animal experimental models that simulate pathophysiology of airway diseases through future studies.

• 대한한방내과학회지
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• 제27권1호
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• pp.126-137
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• 2006

In the present study, the author intended to investigate whether three oriental medical prescriptions named Jeongcheonhwadam-tang(JHT), Haengso-tang(HST), Socheungryong-tang(SCRT) significantly affect mucin release from cultured hamster tracheal surface epithelial (HTSE) cells. The results were as follows: (1) JHT significantly inhibited mucin release from cultured HTSE cells, without significant cytotoxicity : (2) HST significantly inhibited mucin release from cultured HTSE cells, without significant cytotoxicity : (3) SCRT significantly inhibited mucin release from cultured HTSE cells, without significant cytotoxicity : (4) JHT, HST chiefly inhibited the 'mucin' release and did not significantly affect the release of the other releasable glycoproteins with less molecular weight than mucin. These results suggest that the three herbal prescriptions specifically inhibit the release of mucin: (5) JHT significantly inhibited the expression levels of MUC SAC mRNA. This result suggests that JHT affects the synthesis of mucin at gene level in cultured HTSE cells. All agents showed no significant cytotoxicity. In view of these results, further investigation of the effects of JHT and HST are likely to be instrumental in yielding novel agents from oriental medical prescriptions which have inhibitory effects or expectorative effects on airway mucus secretion.

• 대한한방내과학회지
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• 제25권2호
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• pp.238-244
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• 2004

Objective : This study is intended to investigate whether the two oriental medical prescriptions, CheongGeumGangHwa-tang(CGGH) and GwaRuJiSil-tang(GRJS), significantly affect mucin release from cultured hamster tracheal surface epithelial(HTSE) cells. Materials and Methods : Confluent HTSE cells were metabolically radio labeled with 3H-glucosamine for 24 hrs and chased for 30 min in the presence of CGGH or GRJS 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 CGGH and GRJS on contractility of isolated tracheal smooth muscle were investigated. Results : (1) CGGH and GRJS significantly increased mucin release from cultured HTSE cells, without cytotoxicity : (2) CGGH and GRJS did not affect contractility of isolated tracheal smooth muscle. Conclusions : These results suggest that the effects of CGGH and GRJS should be further investigated, and that it would be gainful to invesigate, from among oriental medical prescriptions, what novel agents have these mild expectorant effects on mucin secretion from airway goblet cells.