The Experts below are selected from a list of 3900 Experts worldwide ranked by ideXlab platform

Shaozhen Zhao - One of the best experts on this subject based on the ideXlab platform.

  • The tear fluid Mucin 5AC change of primary angle-closure glaucoma patients after short-term medications and phacotrabeculectomy
    Molecular vision, 2010
    Co-Authors: Wei Liu, Juan Liang, Xiaoli Xing, Aihua Liu, Shaozhen Zhao
    Abstract:

    Purpose: This paper proposed to evaluate the tear fluid Mucin 5AC (MUC5AC) change in Chinese primary angle-closure glaucoma and cataract patients after short-term medications and phacotrabeculectomy. Methods: Twenty-five eyes of 25 consecutive Chinese patients with coexisting visually significant cataract and angleclosure glaucoma and 40 eyes of 40 volunteers enrolled in this study were investigated. Tear fluid from normal subjects and patients (1 day pre-operatively, 1 month, 3 months, and 6 months post-operatively, respectively) were collected. The MUC5AC protein levels in the tear fluid were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The MUC5AC change after phacotrabeculectomy was evaluated. Results: The MUC5AC quantity of the patients after short-term medications was 16.95±12.86 ng/ml, compared with 32.39±18.44 ng/ml MUC5AC quantity of the controls. There was a significant difference between the two groups (p

  • the tear fluid Mucin 5AC change of primary angle closure glaucoma patients after short term medications and phacotrabeculectomy
    Molecular Vision, 2010
    Co-Authors: Wei Liu, Juan Liang, Xiaoli Xing, Aihua Liu, Shaozhen Zhao
    Abstract:

    Purpose: This paper proposed to evaluate the tear fluid Mucin 5AC (MUC5AC) change in Chinese primary angle-closure glaucoma and cataract patients after short-term medications and phacotrabeculectomy. Methods: Twenty-five eyes of 25 consecutive Chinese patients with coexisting visually significant cataract and angleclosure glaucoma and 40 eyes of 40 volunteers enrolled in this study were investigated. Tear fluid from normal subjects and patients (1 day pre-operatively, 1 month, 3 months, and 6 months post-operatively, respectively) were collected. The MUC5AC protein levels in the tear fluid were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The MUC5AC change after phacotrabeculectomy was evaluated. Results: The MUC5AC quantity of the patients after short-term medications was 16.95±12.86 ng/ml, compared with 32.39±18.44 ng/ml MUC5AC quantity of the controls. There was a significant difference between the two groups (p<0.05). The MUC5AC of the patients decreased significantly to 6.91±7.11 ng/ml at 1 month after surgery (p<0.05). At 3 months after surgery, the MUC5AC recovered to 15.53±12.63 ng/ml, and had no significant difference with the pre-operative level (p=0.26). At 6 months after surgery, the MUC5AC was 18.94±14.64 ng/ml and had no significant difference with before-surgery levels (p=0.14). Conclusions: Both phacotrabeculectomy and short-term anti-glaucoma medications can decrease the MUC5AC in the tear fluid of primary angle-closure glaucoma patients. At 3 months after phacotrabeculectomy, the MUC5AC could recover to the pre-operative level. More attention should be paid to the tear film stability and ocular surface physiology in these patients.

Xiangdong Zhou - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA-155 regulates lipopolysaccharide-induced Mucin 5AC overproduction via a suppressor of cytokine signaling 1-mediated mechanism in human bronchial epithelial cells.
    Respiratory physiology & neurobiology, 2019
    Co-Authors: Chunyi Liu, Victor P Kolosov, Xiangdong Zhou, Juliy M Perelman
    Abstract:

    Chronic inflammatory lung diseases accompanied by Gram-negative bacteria infection are characterized by excessive Mucin production. Lipopolysaccharide (LPS), the major endotoxin released from Gram-negative bacteria, is a potent inflammatory agonist for Mucin overproduction. In this study, we sought to examine whether the toll-like receptor (TLR)-responsive microRNA miR-155 plays a role in LPS-provoked induction of Mucin 5AC (MUC5AC) and the potential role of suppressor of cytokine signaling 1 (SOCS1) involved in this process. We found that LPS increased the expression of MUC5AC in association with TLR4-dependent miR-155 induction. The suppression of miR-155 by antagomir led to an excessive production of SOCS1, thereby downregulation of MUC5AC production. Collectively, these data imply that miR-155 is involved in LPS-induced MUC5AC overproduction through a TLR4-dependent manner and thereby the downregulation of SOCS1.

  • Ezrin/Exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Chunyi Liu, Juliy M Perelman, Victor P Kolosov, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • ezrin exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Qi Li, Juliy M Perelman, Victor P Kolosov, Na Li, Rui Xu, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • Glycyrrhizin inhibits human neutrophil elastase-induced Mucin 5AC overproduction in human bronchial epithelial cells
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2014
    Co-Authors: Qingrong Xiao, Xiangdong Zhou
    Abstract:

    OBJECTIVE To investigate the effect of glycyrrhizin (Gly) on human neutrophil elastase (HNE)- induced Mucin (MUC) 5AC overproduction in human bronchial epithelial cells (16HBE), and the potential signaling pathway involved in this process. METHODS The cultured cells were divided into 3 groups: a control group, cultured in serum-free DMEM medium; an HNE group, pretreated with HNE alone; and a Gly group, incubated with HNE and Gly. After stimulation with a variety of Gly concentrations, the cytotoxicity was assessed by methyl thiazolyl tetrazolium method. The mRNA expressions of p38, nuclear factor κB (NF-κB) p65, inhibitory κBα (IκBα) and MUC5AC were detected by real-time PCR. The phosphorylation levels of p38 (p-p38), NF-κB p65 (p-NF-κB p65) and IκBα (p-IκBα) were measured by Western blot while the levels of MUC5AC protein were analyzed by emzyme-linked immunosorbent assay and immunofluorescence. RESULTS Compared with the control group, the expression levels of MUC5AC mRNA and protein in the HNE group were both significantly increased. There was a significant increase in p-p38 and p-NF-κB p65, while the production of IκBα was much lower than that in the control group. Gly significantly inhibited the increase of MUC5AC, p38 and NF-κB p65, but increased the activity of IκBα. CONCLUSION Glycyrrhizin can inhibit MUC5AC overproduction via p38-NF-κB p65/IκBα signaling pathway.

  • Annexin II mediates the neutrophil elastase-stimulated exocytosis of Mucin 5AC.
    Molecular medicine reports, 2013
    Co-Authors: Xiangdong Zhou, Juliy M Perelman, Victor P Kolosov
    Abstract:

    The overexpression and hypersecretion of mucus is a hallmark of several chronic pulmonary inflammatory diseases, including chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. Mucin 5AC (MUC5AC) is a major component of airway mucus. Annexin II (ANXII) has been reported to be expressed in various cells and is associated with the fusion of secretory vesicles. Neutrophil elastase (NE) is present at high concentrations in the airway surface fluid in patients with cystic fibrosis and various other severe diseases. However, the role of ANXII in NE-induced secretion of MUC5AC granules remains unclear. It was determined that NE upregulates the transcription and protein synthesis of ANXII in 16HBE human bronchial epithelial cells. Following stimulation with NE, ANXII is recruited to the cell membrane, as visualised by cell immunochemistry and laser confocal microscopy, and the redistribution of ANXII is inhibited by the protein kinase-C (PKC) inhibitor bisindolylmaleimide I. Conversely, depleting endogenous ANXII decreases MUC5AC secretion into the cell culture supernatant and increases the levels of intracellular MUC5AC protein. The data indicated that ANXII is associated with the secretion of MUC5AC granules.

Wei Liu - One of the best experts on this subject based on the ideXlab platform.

  • The tear fluid Mucin 5AC change of primary angle-closure glaucoma patients after short-term medications and phacotrabeculectomy
    Molecular vision, 2010
    Co-Authors: Wei Liu, Juan Liang, Xiaoli Xing, Aihua Liu, Shaozhen Zhao
    Abstract:

    Purpose: This paper proposed to evaluate the tear fluid Mucin 5AC (MUC5AC) change in Chinese primary angle-closure glaucoma and cataract patients after short-term medications and phacotrabeculectomy. Methods: Twenty-five eyes of 25 consecutive Chinese patients with coexisting visually significant cataract and angleclosure glaucoma and 40 eyes of 40 volunteers enrolled in this study were investigated. Tear fluid from normal subjects and patients (1 day pre-operatively, 1 month, 3 months, and 6 months post-operatively, respectively) were collected. The MUC5AC protein levels in the tear fluid were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The MUC5AC change after phacotrabeculectomy was evaluated. Results: The MUC5AC quantity of the patients after short-term medications was 16.95±12.86 ng/ml, compared with 32.39±18.44 ng/ml MUC5AC quantity of the controls. There was a significant difference between the two groups (p

  • the tear fluid Mucin 5AC change of primary angle closure glaucoma patients after short term medications and phacotrabeculectomy
    Molecular Vision, 2010
    Co-Authors: Wei Liu, Juan Liang, Xiaoli Xing, Aihua Liu, Shaozhen Zhao
    Abstract:

    Purpose: This paper proposed to evaluate the tear fluid Mucin 5AC (MUC5AC) change in Chinese primary angle-closure glaucoma and cataract patients after short-term medications and phacotrabeculectomy. Methods: Twenty-five eyes of 25 consecutive Chinese patients with coexisting visually significant cataract and angleclosure glaucoma and 40 eyes of 40 volunteers enrolled in this study were investigated. Tear fluid from normal subjects and patients (1 day pre-operatively, 1 month, 3 months, and 6 months post-operatively, respectively) were collected. The MUC5AC protein levels in the tear fluid were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The MUC5AC change after phacotrabeculectomy was evaluated. Results: The MUC5AC quantity of the patients after short-term medications was 16.95±12.86 ng/ml, compared with 32.39±18.44 ng/ml MUC5AC quantity of the controls. There was a significant difference between the two groups (p<0.05). The MUC5AC of the patients decreased significantly to 6.91±7.11 ng/ml at 1 month after surgery (p<0.05). At 3 months after surgery, the MUC5AC recovered to 15.53±12.63 ng/ml, and had no significant difference with the pre-operative level (p=0.26). At 6 months after surgery, the MUC5AC was 18.94±14.64 ng/ml and had no significant difference with before-surgery levels (p=0.14). Conclusions: Both phacotrabeculectomy and short-term anti-glaucoma medications can decrease the MUC5AC in the tear fluid of primary angle-closure glaucoma patients. At 3 months after phacotrabeculectomy, the MUC5AC could recover to the pre-operative level. More attention should be paid to the tear film stability and ocular surface physiology in these patients.

Juliy M Perelman - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA-155 regulates lipopolysaccharide-induced Mucin 5AC overproduction via a suppressor of cytokine signaling 1-mediated mechanism in human bronchial epithelial cells.
    Respiratory physiology & neurobiology, 2019
    Co-Authors: Chunyi Liu, Victor P Kolosov, Xiangdong Zhou, Juliy M Perelman
    Abstract:

    Chronic inflammatory lung diseases accompanied by Gram-negative bacteria infection are characterized by excessive Mucin production. Lipopolysaccharide (LPS), the major endotoxin released from Gram-negative bacteria, is a potent inflammatory agonist for Mucin overproduction. In this study, we sought to examine whether the toll-like receptor (TLR)-responsive microRNA miR-155 plays a role in LPS-provoked induction of Mucin 5AC (MUC5AC) and the potential role of suppressor of cytokine signaling 1 (SOCS1) involved in this process. We found that LPS increased the expression of MUC5AC in association with TLR4-dependent miR-155 induction. The suppression of miR-155 by antagomir led to an excessive production of SOCS1, thereby downregulation of MUC5AC production. Collectively, these data imply that miR-155 is involved in LPS-induced MUC5AC overproduction through a TLR4-dependent manner and thereby the downregulation of SOCS1.

  • Ezrin/Exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Chunyi Liu, Juliy M Perelman, Victor P Kolosov, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • ezrin exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Qi Li, Juliy M Perelman, Victor P Kolosov, Na Li, Rui Xu, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • Annexin II mediates the neutrophil elastase-stimulated exocytosis of Mucin 5AC.
    Molecular medicine reports, 2013
    Co-Authors: Xiangdong Zhou, Juliy M Perelman, Victor P Kolosov
    Abstract:

    The overexpression and hypersecretion of mucus is a hallmark of several chronic pulmonary inflammatory diseases, including chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. Mucin 5AC (MUC5AC) is a major component of airway mucus. Annexin II (ANXII) has been reported to be expressed in various cells and is associated with the fusion of secretory vesicles. Neutrophil elastase (NE) is present at high concentrations in the airway surface fluid in patients with cystic fibrosis and various other severe diseases. However, the role of ANXII in NE-induced secretion of MUC5AC granules remains unclear. It was determined that NE upregulates the transcription and protein synthesis of ANXII in 16HBE human bronchial epithelial cells. Following stimulation with NE, ANXII is recruited to the cell membrane, as visualised by cell immunochemistry and laser confocal microscopy, and the redistribution of ANXII is inhibited by the protein kinase-C (PKC) inhibitor bisindolylmaleimide I. Conversely, depleting endogenous ANXII decreases MUC5AC secretion into the cell culture supernatant and increases the levels of intracellular MUC5AC protein. The data indicated that ANXII is associated with the secretion of MUC5AC granules.

  • transient receptor potential vanilloid 1 receptors mediate acid induced Mucin secretion via ca2 influx in human airway epithelial cells
    Journal of Biochemical and Molecular Toxicology, 2012
    Co-Authors: Hongmei Yu, Xiangdong Zhou, Qi Li, Victor P Kolosov, Juliy M Perelman
    Abstract:

    Mucin hypersecretion is a key pathological feature of inflammatory respiratory diseases. Previous studies have reported that acids (gastroesophageal reflux or environmental exposure) induce many respiratory symptoms and are implicated in the pathophysiology of obstructive airway diseases. To understand these mechanisms, we measured acid-induced Mucin secretion in human bronchial epithelial cells. In the present study, acid induced inward currents of transient receptor potential vanilloid (TRPV)1 and Mucin 5AC (MUC5AC) secretion dose dependently, which were inhibited by TRPV1 antagonist capsazepine in a concentration-dependent manner. TRPV1 agonist capsaicin mediated a concentration-dependent increase in TRPV1 inward currents and MUC5AC secretion. Furthermore, capsaicin enhanced acid-induced TRPV1 inward currents and MUC5AC secretion. Acid-induced Ca2+ influx was prevented by capsazepine dose dependently and enhanced by capsaicin. Pretreatment only with capsaicin also increased the Ca2+ concentration in a concentration-dependent manner. These data suggest that pharmacological inhibition of calcium-permeable TRPV1 receptors could be used to prevent acid-induced Mucin secretion, thereby providing a potential mechanism to reduce their toxicity. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:179–186, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20413

Victor P Kolosov - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA-155 regulates lipopolysaccharide-induced Mucin 5AC overproduction via a suppressor of cytokine signaling 1-mediated mechanism in human bronchial epithelial cells.
    Respiratory physiology & neurobiology, 2019
    Co-Authors: Chunyi Liu, Victor P Kolosov, Xiangdong Zhou, Juliy M Perelman
    Abstract:

    Chronic inflammatory lung diseases accompanied by Gram-negative bacteria infection are characterized by excessive Mucin production. Lipopolysaccharide (LPS), the major endotoxin released from Gram-negative bacteria, is a potent inflammatory agonist for Mucin overproduction. In this study, we sought to examine whether the toll-like receptor (TLR)-responsive microRNA miR-155 plays a role in LPS-provoked induction of Mucin 5AC (MUC5AC) and the potential role of suppressor of cytokine signaling 1 (SOCS1) involved in this process. We found that LPS increased the expression of MUC5AC in association with TLR4-dependent miR-155 induction. The suppression of miR-155 by antagomir led to an excessive production of SOCS1, thereby downregulation of MUC5AC production. Collectively, these data imply that miR-155 is involved in LPS-induced MUC5AC overproduction through a TLR4-dependent manner and thereby the downregulation of SOCS1.

  • Ezrin/Exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Chunyi Liu, Juliy M Perelman, Victor P Kolosov, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • ezrin exocyst complex regulates Mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Qi Li, Juliy M Perelman, Victor P Kolosov, Na Li, Rui Xu, Xiangdong Zhou
    Abstract:

    Background/Aim: Increased Mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of Mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in Mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  • Annexin II mediates the neutrophil elastase-stimulated exocytosis of Mucin 5AC.
    Molecular medicine reports, 2013
    Co-Authors: Xiangdong Zhou, Juliy M Perelman, Victor P Kolosov
    Abstract:

    The overexpression and hypersecretion of mucus is a hallmark of several chronic pulmonary inflammatory diseases, including chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. Mucin 5AC (MUC5AC) is a major component of airway mucus. Annexin II (ANXII) has been reported to be expressed in various cells and is associated with the fusion of secretory vesicles. Neutrophil elastase (NE) is present at high concentrations in the airway surface fluid in patients with cystic fibrosis and various other severe diseases. However, the role of ANXII in NE-induced secretion of MUC5AC granules remains unclear. It was determined that NE upregulates the transcription and protein synthesis of ANXII in 16HBE human bronchial epithelial cells. Following stimulation with NE, ANXII is recruited to the cell membrane, as visualised by cell immunochemistry and laser confocal microscopy, and the redistribution of ANXII is inhibited by the protein kinase-C (PKC) inhibitor bisindolylmaleimide I. Conversely, depleting endogenous ANXII decreases MUC5AC secretion into the cell culture supernatant and increases the levels of intracellular MUC5AC protein. The data indicated that ANXII is associated with the secretion of MUC5AC granules.

  • transient receptor potential vanilloid 1 receptors mediate acid induced Mucin secretion via ca2 influx in human airway epithelial cells
    Journal of Biochemical and Molecular Toxicology, 2012
    Co-Authors: Hongmei Yu, Xiangdong Zhou, Qi Li, Victor P Kolosov, Juliy M Perelman
    Abstract:

    Mucin hypersecretion is a key pathological feature of inflammatory respiratory diseases. Previous studies have reported that acids (gastroesophageal reflux or environmental exposure) induce many respiratory symptoms and are implicated in the pathophysiology of obstructive airway diseases. To understand these mechanisms, we measured acid-induced Mucin secretion in human bronchial epithelial cells. In the present study, acid induced inward currents of transient receptor potential vanilloid (TRPV)1 and Mucin 5AC (MUC5AC) secretion dose dependently, which were inhibited by TRPV1 antagonist capsazepine in a concentration-dependent manner. TRPV1 agonist capsaicin mediated a concentration-dependent increase in TRPV1 inward currents and MUC5AC secretion. Furthermore, capsaicin enhanced acid-induced TRPV1 inward currents and MUC5AC secretion. Acid-induced Ca2+ influx was prevented by capsazepine dose dependently and enhanced by capsaicin. Pretreatment only with capsaicin also increased the Ca2+ concentration in a concentration-dependent manner. These data suggest that pharmacological inhibition of calcium-permeable TRPV1 receptors could be used to prevent acid-induced Mucin secretion, thereby providing a potential mechanism to reduce their toxicity. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:179–186, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20413