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1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis.

Sudhoff H, Klenke C, Greiner JF, Müller J, Brotzmann V, Ebmeyer J, Kaltschmidt B, Kaltschmidt C - PLoS ONE (2015)

Bottom Line: Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol.On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity.In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany.

ABSTRACT
Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion.

No MeSH data available.


Related in: MedlinePlus

Increased number of mucus-filled cells in LPS-treated nasal slice cultures is significantly reduced by co-treatment with 1,8-cineol.A: Representative Alcian Blue-staining of an untreated nasal slice culture revealed no increased amount of mucus-filled goblet cells (arrows). B: Representative Alcian Blue-staining of LPS-treated nasal slices showed highly increased numbers of mucus-filled goblet cells (Arrows). C: Representative Alcian Blue-staining of cultured nasal slices co-treated with LPS and 1,8-cineol displayed a highly decreased number of mucus-filled goblet cells (Arrows). Scale Bar: 20 μm. D: Quantification of total areas of Alcian Blue-stained slice cultures from four independent donors revealed a significantly increased number of mucin-filled goblet cells in LPS-treated nasal slice cultures, which was significantly decreased after co-treatment with 1,8-cineol. *p < 0.5, **p < 0.01 were considered significant (t-test); ns: not significant (t-test).
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pone.0133040.g002: Increased number of mucus-filled cells in LPS-treated nasal slice cultures is significantly reduced by co-treatment with 1,8-cineol.A: Representative Alcian Blue-staining of an untreated nasal slice culture revealed no increased amount of mucus-filled goblet cells (arrows). B: Representative Alcian Blue-staining of LPS-treated nasal slices showed highly increased numbers of mucus-filled goblet cells (Arrows). C: Representative Alcian Blue-staining of cultured nasal slices co-treated with LPS and 1,8-cineol displayed a highly decreased number of mucus-filled goblet cells (Arrows). Scale Bar: 20 μm. D: Quantification of total areas of Alcian Blue-stained slice cultures from four independent donors revealed a significantly increased number of mucin-filled goblet cells in LPS-treated nasal slice cultures, which was significantly decreased after co-treatment with 1,8-cineol. *p < 0.5, **p < 0.01 were considered significant (t-test); ns: not significant (t-test).

Mentions: Simulating the presence of a bacterial cell wall, we treated cultivated nasal slices with LPS to determine potential effects of 1,8-cineol on mucin overproduction during experimentally induced late rhinosinusitis [28]. Here, Alcian Blue-staining revealed a highly increased number of mucin-filled goblet cells in cultured tissue after LPS-treatment (Fig 2B, arrows) in contrast to the untreated control approach (Fig 2A, arrows). Notably, the number of mucin-filled goblet cells was decreased in cultured nasal slices treated with LPS and 1,8-cineol (Fig 2C, arrows). Determining these effects in more detail, quantification of mucus-filled goblet cells revealed a significantly increased number of mucin-filled cells after LPS-treatment, which was significantly decreased after co-treatment with 1,8-cineol (Fig 2D). In addition, cultured nasal slices co-treated with LPS and 1,8-cineol showed unchanged low numbers of Caspase 3-expressing cells compared to untreated and LPS-treated cultures as well as to inferior turbinate tissue, suggesting unaffected viability of the cultured nasal tissue (S1 Fig).


1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis.

Sudhoff H, Klenke C, Greiner JF, Müller J, Brotzmann V, Ebmeyer J, Kaltschmidt B, Kaltschmidt C - PLoS ONE (2015)

Increased number of mucus-filled cells in LPS-treated nasal slice cultures is significantly reduced by co-treatment with 1,8-cineol.A: Representative Alcian Blue-staining of an untreated nasal slice culture revealed no increased amount of mucus-filled goblet cells (arrows). B: Representative Alcian Blue-staining of LPS-treated nasal slices showed highly increased numbers of mucus-filled goblet cells (Arrows). C: Representative Alcian Blue-staining of cultured nasal slices co-treated with LPS and 1,8-cineol displayed a highly decreased number of mucus-filled goblet cells (Arrows). Scale Bar: 20 μm. D: Quantification of total areas of Alcian Blue-stained slice cultures from four independent donors revealed a significantly increased number of mucin-filled goblet cells in LPS-treated nasal slice cultures, which was significantly decreased after co-treatment with 1,8-cineol. *p < 0.5, **p < 0.01 were considered significant (t-test); ns: not significant (t-test).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4514714&req=5

pone.0133040.g002: Increased number of mucus-filled cells in LPS-treated nasal slice cultures is significantly reduced by co-treatment with 1,8-cineol.A: Representative Alcian Blue-staining of an untreated nasal slice culture revealed no increased amount of mucus-filled goblet cells (arrows). B: Representative Alcian Blue-staining of LPS-treated nasal slices showed highly increased numbers of mucus-filled goblet cells (Arrows). C: Representative Alcian Blue-staining of cultured nasal slices co-treated with LPS and 1,8-cineol displayed a highly decreased number of mucus-filled goblet cells (Arrows). Scale Bar: 20 μm. D: Quantification of total areas of Alcian Blue-stained slice cultures from four independent donors revealed a significantly increased number of mucin-filled goblet cells in LPS-treated nasal slice cultures, which was significantly decreased after co-treatment with 1,8-cineol. *p < 0.5, **p < 0.01 were considered significant (t-test); ns: not significant (t-test).
Mentions: Simulating the presence of a bacterial cell wall, we treated cultivated nasal slices with LPS to determine potential effects of 1,8-cineol on mucin overproduction during experimentally induced late rhinosinusitis [28]. Here, Alcian Blue-staining revealed a highly increased number of mucin-filled goblet cells in cultured tissue after LPS-treatment (Fig 2B, arrows) in contrast to the untreated control approach (Fig 2A, arrows). Notably, the number of mucin-filled goblet cells was decreased in cultured nasal slices treated with LPS and 1,8-cineol (Fig 2C, arrows). Determining these effects in more detail, quantification of mucus-filled goblet cells revealed a significantly increased number of mucin-filled cells after LPS-treatment, which was significantly decreased after co-treatment with 1,8-cineol (Fig 2D). In addition, cultured nasal slices co-treated with LPS and 1,8-cineol showed unchanged low numbers of Caspase 3-expressing cells compared to untreated and LPS-treated cultures as well as to inferior turbinate tissue, suggesting unaffected viability of the cultured nasal tissue (S1 Fig).

Bottom Line: Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol.On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity.In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany.

ABSTRACT
Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion.

No MeSH data available.


Related in: MedlinePlus