ABSTRACT
Objectives@#. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs). @*Methods@#. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining. @*Results@#. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. @*Conclusion@#. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.
ABSTRACT
Empty nose syndrome is a rare complication caused by excessive removal of normal tissues after nose surgery. The main symptoms of empty nose syndrome are paradoxical nasal obstruction, dryness, crust and dyspnea. Medical treatments such as irrigation, humidification, and ointment are not very effective, so surgical treatments to reconstruct the normal nasal cavity using implant materials are often considered. If the implant is not properly inserted, the symptoms persist and the implant must be removed again, resulting in the only donor site complications. Therefore, it is essential to treat the implant well and insert it precisely. Here we describe a surgical procedure to manage implant materials using autologous costal cartilage in the form of block, diced, and crushed cartilage for augmentation technique.
ABSTRACT
Background and Objectives@#Peroxiredoxin (Prx) is an antioxidant enzyme involved in signaling pathway. Prx2 is the most abundant in mammalian gray matter neurons and has protective role under oxidative stress. MUC5AC and MUC5B are typical mucin genes in human airway epithelial cells. Even if free radicals play a key role in chronic respiratory inflammatory diseases, the effects of the Prx2 on mucin expression and oxidative stress are not clearly known. The purpose of this study is to investigate the effect of Prx2 on lipopolysaccharide (LPS)-induced MUC5AC/5B expression and reactive oxygen species (ROS) in human airway epithelial cells.Subjects and Method In NCI-H292 cells and human nasal epithelial cells, the effects of Prx2 on LPS-induced MUC5AC/5B expression and ROS production were investigated using reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, enzyme linked immunosorbent assay (ELISA) and flow cytometry analysis. @*Results@#MUC5AC, MUC5B mRNA expression and protein production were increased by LPS. ROS production was also increased by LPS. Prx2 suppressed the LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. However, Prx2 did not inhibit MUC5B mRNA expression and protein production. N-acetylcysteine, diphenyleneiodonium, and apocynin also inhibited LPS-induced ROS production. @*Conclusion@#These results may show that Prx2 suppresses LPS-induced MUC5AC expression via ROS in human airway epithelial cells.
ABSTRACT
Background and Objectives@#Ginsenoside Rb1 is the main metabolite of Panax ginseng. It is known to have many beneficial properties including anti-inflammatory, antitumoral and antioxidant effects. However, the therapeutic effects of ginenoside Rb1 on inflammatory airway diseases have not been elucidated. Therefore, we investigated the effects of ginsenoside Rb1 on the TGF-β1-induced mucin gene expression and epithelial-mesenchymal transition (EMT) in human airway epithelial cells.Materials and Method We evaluated the effects of ginsenoside Rb1 on the changes of MUC4, MUC5AC, occludin, claudin 4, claudin 18, neural (N)-cadherin, and epithelial (E)-cadherin expression by TGF-β1 in NCI-H292 cells using reverse, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot. @*Results@#TGF-β1 significantly increased MUC4/5AC expression. Rb1 inhibited TGF-β1- induced MUC4/5AC expression. In addition, TGF-β1 significantly attenuated occludin, claudin 18, and E-cadherin expressions but induced claudin 4 and N-cadherin expressions. On the other hand, Rb1 reversed changes in the TGF-β1- mediated expressions of cell junction molecules. @*Conclusion@#These results suggest that ginsenoside Rb1 attenuates TGF-β1-induced MUC4/5AC expressions and EMT in the human airway epithelial cells. These findings are important data demonstrating the potential of ginsenoside Rb1 as a therapeutic agent for inflammatory airway diseases.
ABSTRACT
Objectives@#. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial. @*Methods@#. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA. @*Results@#. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells. @*Conclusion@#. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.
ABSTRACT
Objectives@#. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial. @*Methods@#. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA. @*Results@#. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells. @*Conclusion@#. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.
ABSTRACT
Background and Objectives@#Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to investigate the effect of TSNAs on mucin overexpression and its molecular mechanism in human airway epithelial cells.Materials and Method: The cytotoxicity of TSNAs was evaluated using EX-Cytox and inverted microscopy. The mRNA and protein levels of MUC5AC and MUC5B were measured using real-time PCR and ELISA. @*Results@#NAB, NNN, NNAL, and NNK did not affect cell viability. NAT did not affect cell viability up to a concentration of 100 μM in human airway epithelial cells. NAT, NNN, NNAL, and NNK significantly induced MUC5AC expression, but not MUC5B expression. NAB did not affect the expression of MUC5AC and MUC5B. Propranolol (a β-adrenergic receptor antagonist) inhibited NAT, NNN, NNAL, and NNK-induced MUC5AC expression, whereas α-bungarotoxin (an α7-nicotinic acetylcholine receptor antagonist) only inhibited NNN- and NNK-induced MUC5AC expression. @*Conclusion@#These results suggested that NAT, NNN, NNAL, and NNK induce MUC5AC expression through β-adrenergic receptor and/or α7-nicotinic acetylcholine receptor in human airway epithelial cells, which may be involved in mucus hypersecretion in inflammatory airway diseases.
ABSTRACT
Active and prompt scale-up screening tests are essential to efficiently control the coronavirus disease 2019 (COVID-19) outbreak. The goal of this work was to identify shortcomings in the conventional screening system (CSS) implemented in the beginning of the outbreak. To overcome these shortcomings, we then introduced a novel, independently developed system called the Yeungnam University type drive-through (YU-Thru), and distributed it nationwide in Korea. This system is similar to the drive-throughs utilized by fast food restaurants. YU-Thru system has shortened the time taken to test a single person to 2–4 minutes, by completely eliminating the time required to clean and ventilate the specimen collection room. This time requirement was a major drawback of the CSS. YU-Thru system also reduced the risk of subjects and medical staff infecting one another by using a separate and closed examination system. On average, 50 to 60 tests were conducted per day when using the CSS, while now up to 350 tests per day are conducted with the YU-Thru system. We believe that the YU-Thru system has made an important contribution to the rapid detection of COVID-19 in Daegu, South Korea. Here, we will describe the YU-Thru system in detail so that other countries experiencing COVID-19 outbreaks can take advantage of this system.
ABSTRACT
OBJECTIVES: Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. METHODS: In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptasepolymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. RESULTS: Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. CONCLUSION.: These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.
Subject(s)
Humans , Activating Transcription Factor 6 , Carrier Proteins , CCAAT-Enhancer-Binding Proteins , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Epithelial Cells , Glycoproteins , Immunoenzyme Techniques , Inositol , Mucins , Phosphotransferases , Real-Time Polymerase Chain Reaction , RNA, Messenger , RNA, Small Interfering , Transcription Factor CHOP , Transcription Factors , Transfection , TunicamycinABSTRACT
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.
Subject(s)
Humans , Acetylcysteine , Epithelial Cells , Epithelium , Immunoenzyme Techniques , Methods , Mucins , Mucus , NADP , Oxidative Stress , Oxidoreductases , Panax , Reactive Oxygen Species , RNA, MessengerABSTRACT
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.
Subject(s)
Humans , B-Lymphocytes , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Lubrication , Methods , Mortality , Mucins , Mucus , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Phosphotransferases , Protein Kinases , RNA, MessengerABSTRACT
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.
ABSTRACT
OBJECTIVES: Clusterin (CLU) is known as apolipoprotein J, and has three isoforms with different biological functions. CLU is associated with various diseases such as Alzheimer disease, atherosclerosis, and some malignancies. Recent studies report an association of CLU with inflammation and immune response in inflammatory airway diseases. However, the effect of CLU on mucin secretion of airway epithelial cells has not yet been understood. Therefore, the effect and brief signaling pathway of CLU on MUC5AC (as a major secreted mucin) expression were investigated in human airway epithelial cells. METHODS: In the tissues of nasal polyp and normal inferior turbinate, the presence of MUC5AC and CLU was investigated using immunohistochemical stain and Western blot analysis. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway of CLU on MUC5AC expression were investigated using immunohistochemical stain, reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and Western blot analysis. RESULTS: In the nasal polyps, MUC5AC and CLU were abundantly present in the epithelium on immunohistochemical stain, and nuclear CLU (nCLU) was strongly detected on Western blot analysis. In human NCI-H292 airway epithelial cells or the primary cultures of normal nasal epithelial cells, recombinant nCLU increased MUC5AC expression, and significantly activated phosphorylation of NF-κB. And BAY 11-7085 (a specific NF-κB inhibitor) and knockdown of NF-κB by NF-κB siRNA (small interfering RNA) significantly attenuated recombinant nCLU-induced MUC5AC expression. CONCLUSION: These results suggest that nCLU induces MUC5AC expression via the activation of NF-κB signaling pathway in human airway epithelial cells.
Subject(s)
Humans , Alzheimer Disease , Atherosclerosis , B-Lymphocytes , Bays , Blotting, Western , Clusterin , Epithelial Cells , Epithelium , Immunoenzyme Techniques , Inflammation , Mucins , Nasal Polyps , NF-kappa B , Phosphorylation , Protein Isoforms , Real-Time Polymerase Chain Reaction , RNA, Small Interfering , TurbinatesABSTRACT
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.
Subject(s)
Humans , Arthritis, Rheumatoid , Asthma , Blotting, Western , Epithelial Cells , Immunoenzyme Techniques , Lupus Erythematosus, Systemic , Medicine, Chinese Traditional , Methods , Mucins , Nephritis , NF-kappa B , Phosphorylation , Real-Time Polymerase Chain Reaction , RNA, Messenger , SaponinsABSTRACT
BACKGROUND: Saccade test, smooth pursuit test, and optokinetic nystagmus test are clinically useful tests to accurately diagnose vertigo. However, there have only been a few studies regarding a correlation between the anatomical site of the lesion and the abnormality of eyeball movement in patients with vertigo.METHODS: The medical records of 97 patients with vertigo between January 2006 and June 2008 were reviewed retrospectively. We classified many kinds of abnormalities regarding the saccade test, smooth pursuit test and optokinetic nystagmus test into several categories and analyzed the localizing lesion of vertigo.RESULTS: According to the saccade test, both total saccade abnormality (S-total) and slow velocity of saccade (S-type 3) were shown to be significantly higher in the central lesion of vertigo. According to the smooth pursuit test, symmetrical unidirectional smooth pursuit abnormality (SP-type 2) was observed to be significantly higher in the peripheral lesion over vertigo. Moreover, according to the optokinetic nystagmus test, total optokinetic nystagmus abnormalities (OKN-total) were shown to be significantly useful findings in the diagnosis of the central lesion of vertigo. The coexisting abnormalities of all three tests (S+SP+OKN abnormalities) were shown to be significantly higher in the central lesion of vertigo.CONCLUSION: These results suggest that all these tests, saccade test, smooth pursuit test, and optokinetic nystagmus test, are very useful to distinguish between the central lesion and the peripheral lesion of vertigo. However, these tests are not beneficial in localizing the central lesion of vertigo.
Subject(s)
Humans , Diagnosis , Medical Records , Nystagmus, Optokinetic , Pursuit, Smooth , Retrospective Studies , Saccades , VertigoABSTRACT
BACKGROUND AND OBJECTIVES: The effects of hyperglycemia on the mucin secretion in inflammatory respiratory diseases are not clear. Therefore, this study was conducted to characterize the effect of hyperglycemia, and the mechanism involved, on 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 exposed to different concentration of glucose (5, 10, 15, 20, 30 mM) for 8 or 24 hours, the effects of high concentration of glucose (20 mM) on MUC5AC and MUC5B expression were determined using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR and enzyme immunoassay. Measurement of reactive oxygen species (ROS) production was performed by flow cytometry. To investigate the role of ROS in high concentration of glucose-induced MUC5B expression, the cells were pretreated with N-acetyl-cysteine (NAC, 50 mM) as a ROS scavenger, or diphenyleneiodonium (DPI, 100 nM) as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor for 1 hour. RESULTS: In the NCI-H292 cells and the primary cultures of human nasal epithelial cells, High concentration of glucose increased MUC5B expression but did not increase MUC5AC expression (p<0.05). ROS production was also increased by high concentration of glucose (20 mM) (p<0.05). In addition, high concentration of glucose (20 mM)-induced MUC5B expression and ROS production were significantly attenuated by pretreatment of NAC (50 mM) or DPI (100 nM) (p<0.05). CONCLUSION: High concentration of glucose induces MUC5B expressions via ROS in human airway epithelial cells.
Subject(s)
Humans , Epithelial Cells , Flow Cytometry , Glucose , Hyperglycemia , Immunoenzyme Techniques , Methods , Mucins , NADP , Oxidoreductases , Reactive Oxygen Species , Real-Time Polymerase Chain ReactionABSTRACT
Malignancy of the external auditory canal (EAC) is a rare tumor. Among the malignancies of EAC, squamous cell carcinoma (SCC) is the most common pathologic type. The causes of SCC of EAC may be exposure to ultraviolet rays, cholesteatoma, chronic otitis externa, and rarely radiotherapy. SCC of EAC has the diverse and non-specific clinical features including mass of tissue, otorrhea, otalgia, tinnitus, and facial palsy which make it difficult to distinguish between SCC and benign tumor. Recently, we experienced a case of SCC of EAC occurred in the left external auditory canal after radiotherapy for Kimura's disease, which was misdiagnosed as keratoacanthoma at first. The findings of this case suggest that when it is difficult to distinguish SCC from benign tumor of EAC, the excisional biopsy including enough resected margin and base of tumor is needed for an exact diagnosis.
Subject(s)
Biopsy , Carcinoma, Squamous Cell , Cholesteatoma , Diagnosis , Ear Canal , Earache , Epithelial Cells , Facial Paralysis , Keratoacanthoma , Otitis Externa , Radiotherapy , Tinnitus , Ultraviolet RaysABSTRACT
BACKGROUND AND OBJECTIVES: Asian sand dust (ASD) is a meteorological phenomenon that occurs in spring time in Korea. ASD is composed of various organic and inorganic materials, which induce airway inflammation. MUC4 is an important membrane-bound mucin gene in the human airway, and its expression is increased in pathologic proliferative lesions such as nasal polyps. However, the effect of ASD on MUC4 in human airway epithelial cells is unclear. Therefore, this study aimed to investigate the effect and signaling pathway of ASD on MUC4 expressions in human airway epithelial cells. METERIALS AND METHOD: The effect and signaling pathway of ASD on MUC4 expressions were investigated in NCI-H292 cells and in the primary cultures of human nasal epithelial cells using reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering ribonucleic acid (siRNA). RESULTS: ASD induced MUC4 expression and the activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). An ERK1/2 MAPK inhibitor and a p38 MAPK inhibitor inhibited the ASD-induced MUC4 expression. In addition, the knockdowns of ERK1, ERK2 and p38 MAPK by the respective siRNA blocked the ASD-induced MUC4 mRNA expression. ASD induced toll-like receptor 4 (TLR4) mRNA expression. The knockdown of TLR4 by TLR4 siRNA blocked the phosphorylation of ERK1/2 and p38 MAPK, and the ASD-induced MUC4 mRNA expression. CONCLUSION: These results show that ASD induces MUC4 expressions via TLR4-dependent ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.
Subject(s)
Humans , Humans , Asian People , Dust , Epithelial Cells , Immunoenzyme Techniques , Inflammation , Korea , Methods , Mucins , Nasal Polyps , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Phosphotransferases , Protein Kinases , Real-Time Polymerase Chain Reaction , RNA , RNA, Messenger , RNA, Small Interfering , Toll-Like Receptor 4ABSTRACT
BACKGROUND: Saccade test, smooth pursuit test, and optokinetic nystagmus test are clinically useful tests to accurately diagnose vertigo. However, there have only been a few studies regarding a correlation between the anatomical site of the lesion and the abnormality of eyeball movement in patients with vertigo. METHODS: The medical records of 97 patients with vertigo between January 2006 and June 2008 were reviewed retrospectively. We classified many kinds of abnormalities regarding the saccade test, smooth pursuit test and optokinetic nystagmus test into several categories and analyzed the localizing lesion of vertigo. RESULTS: According to the saccade test, both total saccade abnormality (S-total) and slow velocity of saccade (S-type 3) were shown to be significantly higher in the central lesion of vertigo. According to the smooth pursuit test, symmetrical unidirectional smooth pursuit abnormality (SP-type 2) was observed to be significantly higher in the peripheral lesion over vertigo. Moreover, according to the optokinetic nystagmus test, total optokinetic nystagmus abnormalities (OKN-total) were shown to be significantly useful findings in the diagnosis of the central lesion of vertigo. The coexisting abnormalities of all three tests (S+SP+OKN abnormalities) were shown to be significantly higher in the central lesion of vertigo. CONCLUSION: These results suggest that all these tests, saccade test, smooth pursuit test, and optokinetic nystagmus test, are very useful to distinguish between the central lesion and the peripheral lesion of vertigo. However, these tests are not beneficial in localizing the central lesion of vertigo.
Subject(s)
Humans , Diagnosis , Medical Records , Nystagmus, Optokinetic , Pursuit, Smooth , Retrospective Studies , Saccades , VertigoABSTRACT
OBJECTIVES: Excessive production of mucus results in plugging of the airway tract, which can increase morbidity and mortality in affected patients. In patients with diabetes, inflammatory airway disease appears with more frequent relapse and longer duration of symptoms. However, the effects of high glucose (HG) on the secretion of mucin in inflammatory respiratory diseases are not clear. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of HG on MUC5B expression in human airway epithelial cells. METHODS: The effect and signaling pathway of HG on MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA. RESULTS: HG increased MUC5B expression and epidermal growth factor receptor (EGFR) expression, and activated the phosphorylation of EGFR and p38 mitogen-activated protein kinase (MAPK). Pretreatment with EGFR inhibitor significantly attenuated the HG-induced phosphorylation of p38 MAPK, and pretreatments with p38 inhibitor or EGFR inhibitor significantly attenuated HG-induced MUC5B expression. In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked HG-induced MUC5B expression. CONCLUSION: These findings suggest that HG induces MUC5B expression via the sequential activations of the EGFR/p38 MAPK signaling pathway in human airway epithelial cells.