1.Betulin, an Anti-Inflammatory Triterpenoid Compound, Regulates MUC5AC Mucin Gene Expression through NF-kB Signaling in Human Airway Epithelial Cells
Rajib HOSSAIN ; Kyung-il KIM ; Fengri JIN ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2022;30(6):540-545
Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription -polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.
2.Kaempferol Regulates the Expression of Airway MUC5AC Mucin Gene via IκBα-NF-κB p65 and p38-p44/42-Sp1 Signaling Pathways
Xin LI ; Fengri JIN ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2021;29(3):303-310
In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.
3.Kaempferol Regulates the Expression of Airway MUC5AC Mucin Gene via IκBα-NF-κB p65 and p38-p44/42-Sp1 Signaling Pathways
Xin LI ; Fengri JIN ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2021;29(3):303-310
In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.
4.Recent Advances in the Development of Novel Drug Candidates for Regulating the Secretion of Pulmonary Mucus
Xin LI ; Fengri JIN ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2020;28(4):293-301
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.
5.Diclofenac Inhibits Phorbol Ester-Induced Gene Expression and Production of MUC5AC Mucin via Affecting Degradation of IkBα and Translocation of NF-kB p65 in NCI-H292 Cells
Fengri JIN ; Xin LI ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2020;28(5):431-436
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.