Effect of Resolvin D1 and E1 on Mucin Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin is an important component of mucus that performs the first line of defense against inhaled pathogens and particles, lubrication of organs, and protection of airway. It is hyper-secreted in inflammatory airway diseases and is associated with morbidity and mortality of the affected patients. Resolvin, an autacoid of a specific lipid structure, exhibits anti-inflammatory property against inflammatory airway diseases although its effects on mucin secretion by human airway epithelial cells have not yet been demonstrated. In this regard, we investigated the effects of Resolvin on lipopolysaccharide (LPS)-induced mucin expression in human airway epithelial cells. MATERIALS AND METHOD: In mucin-producing human NCI-H292 epithelial cells, the effects and brief signaling pathways of Resolvin D1 (RvD1) and Resolvin E1 (RvE1) on the LPS-induced MUC4, MUC5AC, and MUC5B expression were investigated using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: RvD1 attenuated LPS-induced MUC4, MUC5AC, and MUC5B mRNA expression and protein production in human NCI-H292 cells while RvE1 did not. RvD1 significantly blocked LPS-induced activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while RvE1 did not. CONCLUSION: These results suggest that RvD1 attenuates LPS-induced MUC4, MUC5AC, and MUC5B expressions via ERK1/2 MAPK, p38 MAPK, and NF-κB signaling pathways in airway epithelial cells. Therefore, RvD1 may modulate the control of mucus-hypersecretion in inflammatory airway diseases.

Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MUC5AC is one of the major secretory mucin genes in the human airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to have anti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucin secretion of airway epithelial cells still have not been reported. Therefore, the aim of this study is to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expression in human airway epithelial cells. MATERIALS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerase chain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC) as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPS-induced ROS production in human NCI-H292 cells. RESULTS: LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. In addition, NAC and apocynin inhibited LPS-induced MUC5AC mRNA expression and protein production. CONCLUSION: These results demonstrate that PPD inhibits LPS-induced MUC5AC expression via ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that of NAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control of mucus secretion and oxidative stress in human airway epithelial cells.

Triptolide Inhibits Lipopolysaccharide-Induced MUC5AC/5B Expression via Nuclear Factor-Kappa B in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The representative mucin genes in the human airway are MUC5AC and MUC5B, which are regulated by several inflammatory and anti-inflammatory substances. Triptolide (TPL), udenafil, betulinic acid, changkil saponin, and glucosteroid are some of the many anti-inflammatory substances that exist. TPL is a diterpenoid compound from the thunder god vine, which is used in traditional Chinese medicine for treatment of immune inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. However, the effects of TPL on mucin expression of human airway epithelial cells have yet to be reported. Hence, this study investigated the effect of TPL on lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expression in human airway epithelial cells. SUBJECTS AND METHOD: The NCI-H292 cells and the primary cultures of human nasal epithelial cells were used to investigate the effects of TPL on LPS-induced MUC5AC and MUC5B expression using real-time polymerase chain reaction, enzyme immunoassay, and Western blot. RESULTS: TPL significantly decreased the LPS-induced MUC5AC and MUC5B mRNA expression and protein production. TPL also significantly decreased the nuclear factor-kappa B (NF-kB) phosphorylation. CONCLUSION: These results suggest that TPL down regulates MUC5AC and MUC5B expression via inhibition of NF-kB activation in human airway epithelial cells. This study may provide important information about the biological role of triptolide on mucus-secretion in airway inflammatory diseases and the development of novel therapeutic agents for controlling such diseases.

Effect of Polyinosinic-Polycytidylic Acid on MUC5B Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Polyinosinic-polycytidylic acid (Poly I:C) is structurally similar to double-stranded RNA, and is known to induce various inflammatory mediators and to cause inflammatory reactions in airway epithelial cells. However, the effect of Poly I:C on secretion of mucins in human airway epithelial cells has been very rarely reported. In this study, the effect and brief signaling pathway of Poly I:C on the expression of mucin genes were investigated in human airway epithelial cells. MATERIALS AND METHOD: In mucin-producing human NCI-H292 airway epithelial cells and the primary cultures of normal human nasal epithelial cells, the effect and signaling pathway of Poly I:C on expression of mucin genes were investigated using reverse transcriptase-polymerase chain reaction, real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA) for mitogen-activated protein kinase (MAPK). RESULTS: Poly I:C induced the MUC5B expression, and activated the phosphorylation of ERK1/2 and p38 MAPK. U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited the Poly I:C-induced MUC5B expression. In addition, the knockdown of ERK2 and p38 MAPK by siRNA significantly blocked the Poly I:C-induced MUC5B mRNA expression. CONCLUSION: Poly I:C induces the MUC5B expression via ERK2 and p38 MAPK signaling pathways in human airway epithelial cells. Therefore, Poly I:C may play a role in the regulation of mucus hypersecretion through MAPK signaling pathways in the human airway epithelial cells.

Effect of Multi-Walled Carbon Nanotubes on MUC5AC and MUC5B Expression in Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Multi-walled carbon nanotubes (MWCNT) are one of the most commonly used nanomaterials to date. Recent studies have demonstrated that MWCNT increase immune response and allergic inflammation in airway epithelial cells. However, the effects of MWCNT on mucin in human airway epithelial cells have not been reported. Therefore, in the present study, the effect of MWCNT on MUC16, MUC5AC, and MUC5B expressions were investigated in human airway epithelial cells. SUBJECTS AND METHOD: In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effects of MWCNT on MUC16, MUC5AC, and MUC5B expression were analyzed by reverse transcription polymerase chain reaction, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: In human NCI-H292 airway epithelial cells, MWCNT significantly induced the expression MUC5AC and MUC5B mRNA and the production of MUC5AC and MUC5B protein. However, MWCNT did not induce the expression of MUC16 mRNA. In the primary cultures of normal nasal epithelial cells, MWCNT also induced the expression of MUC5AC and MUC5B mRNA and the production of MUC5AC and MUC5B proteins. CONCLUSION: The results of this study demonstrate that MWCNT induces MUC5AC and MUC5B expression in human airway epithelial cells. These findings provide important information about the biological role of MWCNT on mucus-secretion in human airway epithelial cells.

Effect of Betulinic Acid on MUC5AC and MUC5B Expression in Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MUC5AC and MUC5B are representative secretory mucin genes in the human airway, whose expressions are increased by a variety of inflammatory mediators. Betulinic acid, a naturally occurring pentacyclic triterpenoid, is known to have an anti-inflammatory property. However, the effects of betulinic acid on mucin secretion of airway epithelial cells still have not been reported. Therefore, in this study, the effect of betulinic acid on inflammatory mediators-induced MUC5AC and MUC5B expressions was investigated in human airway epithelial cells. SUBJECTS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effects of betulinic acid on interleukin-1beta (IL-1beta)-, lipopolysaccharide (LPS)-, and phorbol myristate acetate (PMA)-induced MUC5AC and MUC5B expressions were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Betulinic acid attenuated IL-1beta-, LPS-, and PMA-induced MUC5B mRNA and glycoprotein expression in NCI-H292 cells. On the other hand, betulinic acid did not attenuate IL-1beta-, and LPS-, but induced PMA-induced MUC5AC mRNA and glycoprotein expressions in NCI-H292 cells. CONCLUSION: These results suggest that betulinic acid attenuates IL-1beta-, LPS-, and PMA-induced MUC5B expression in the airway epithelial cells. Therefore, betulinic acid may modulate a control of mucus-hypersecretion in airway inflammatory diseases.