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Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin-induced murine model of asthma.

Liou CJ, Cheng PY, Huang WC, Chan CC, Chen MC, Kuo ML, Shen JJ - Allergy Asthma Immunol Res (2014)

Bottom Line: Lovastatin is an effective inhibitor of cholesterol synthesis.However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes.Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan. ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.

ABSTRACT

Purpose: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.

Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro.

Results: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells.

Conclusions: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.

No MeSH data available.


Related in: MedlinePlus

Lovastatin suppression of eosinophil adhesion to BEAS-2B cells. HL-60 cells were treated with calcein AM and applied to BEAS-2B cell cultures. Results were observed using fluorescence microscopy. Note the adherence of HL-60 cells to normal (A) and TNF-α-activated BEAS-2B cells (B). Pretreatment of HL-60 cells with 10 µM (C), 20 µM (D), and 40 µM (E) of lovastatin reduced the adherence of HL-60 cells to BEAS-2B cells in a dose-dependent manner.
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Figure 6: Lovastatin suppression of eosinophil adhesion to BEAS-2B cells. HL-60 cells were treated with calcein AM and applied to BEAS-2B cell cultures. Results were observed using fluorescence microscopy. Note the adherence of HL-60 cells to normal (A) and TNF-α-activated BEAS-2B cells (B). Pretreatment of HL-60 cells with 10 µM (C), 20 µM (D), and 40 µM (E) of lovastatin reduced the adherence of HL-60 cells to BEAS-2B cells in a dose-dependent manner.

Mentions: In the present study, we found that lovastatin decreased the expression of ICAM-1 and eotaxins, proteins that promote adhesion of eosinophils to inflammatory BEAS-2B cells. Next, we investigated whether lovastatin could suppress the adhesion of eosinophil-like HL-60 cells to inflammatory BEAS-2B cells (Fig. 6). Calcein AM was used to visualize cell-cell adhesion. TNF-α-stimulation resulted in increased adhesion of HL-60 cells to BEAS-2B cultures. Pretreatment with lovastatin, however, inhibited this adhesion significantly.


Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin-induced murine model of asthma.

Liou CJ, Cheng PY, Huang WC, Chan CC, Chen MC, Kuo ML, Shen JJ - Allergy Asthma Immunol Res (2014)

Lovastatin suppression of eosinophil adhesion to BEAS-2B cells. HL-60 cells were treated with calcein AM and applied to BEAS-2B cell cultures. Results were observed using fluorescence microscopy. Note the adherence of HL-60 cells to normal (A) and TNF-α-activated BEAS-2B cells (B). Pretreatment of HL-60 cells with 10 µM (C), 20 µM (D), and 40 µM (E) of lovastatin reduced the adherence of HL-60 cells to BEAS-2B cells in a dose-dependent manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214976&req=5

Figure 6: Lovastatin suppression of eosinophil adhesion to BEAS-2B cells. HL-60 cells were treated with calcein AM and applied to BEAS-2B cell cultures. Results were observed using fluorescence microscopy. Note the adherence of HL-60 cells to normal (A) and TNF-α-activated BEAS-2B cells (B). Pretreatment of HL-60 cells with 10 µM (C), 20 µM (D), and 40 µM (E) of lovastatin reduced the adherence of HL-60 cells to BEAS-2B cells in a dose-dependent manner.
Mentions: In the present study, we found that lovastatin decreased the expression of ICAM-1 and eotaxins, proteins that promote adhesion of eosinophils to inflammatory BEAS-2B cells. Next, we investigated whether lovastatin could suppress the adhesion of eosinophil-like HL-60 cells to inflammatory BEAS-2B cells (Fig. 6). Calcein AM was used to visualize cell-cell adhesion. TNF-α-stimulation resulted in increased adhesion of HL-60 cells to BEAS-2B cultures. Pretreatment with lovastatin, however, inhibited this adhesion significantly.

Bottom Line: Lovastatin is an effective inhibitor of cholesterol synthesis.However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes.Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan. ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.

ABSTRACT

Purpose: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.

Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro.

Results: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells.

Conclusions: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.

No MeSH data available.


Related in: MedlinePlus