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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

Effects of lovastatin on eosinophil infiltration in lung tissue. Hematoxylin and eosin staining of lung tissue from normal (A), OVA (B), L10 (C), and L40 (D) groups (200×magnification). Arrows indicate areas with peribronchial and perivascular eosinophils.
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Figure 4: Effects of lovastatin on eosinophil infiltration in lung tissue. Hematoxylin and eosin staining of lung tissue from normal (A), OVA (B), L10 (C), and L40 (D) groups (200×magnification). Arrows indicate areas with peribronchial and perivascular eosinophils.

Mentions: Eotaxins induce migration of eosinophils into the lungs.3 Real-time PCR analysis showed that lovastatin decreased expression of eotaxins, including CCL11 and CCL24. Hematoxylin and eosin (H&E) staining of lung sections revealed that OVA-sensitized mice exhibit more eosinophil infiltration between the trachea and the blood vessels than normal control mice (Fig. 4). This infiltration was significantly suppressed by lovastatin treatment.


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)

Effects of lovastatin on eosinophil infiltration in lung tissue. Hematoxylin and eosin staining of lung tissue from normal (A), OVA (B), L10 (C), and L40 (D) groups (200×magnification). Arrows indicate areas with peribronchial and perivascular eosinophils.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effects of lovastatin on eosinophil infiltration in lung tissue. Hematoxylin and eosin staining of lung tissue from normal (A), OVA (B), L10 (C), and L40 (D) groups (200×magnification). Arrows indicate areas with peribronchial and perivascular eosinophils.
Mentions: Eotaxins induce migration of eosinophils into the lungs.3 Real-time PCR analysis showed that lovastatin decreased expression of eotaxins, including CCL11 and CCL24. Hematoxylin and eosin (H&E) staining of lung sections revealed that OVA-sensitized mice exhibit more eosinophil infiltration between the trachea and the blood vessels than normal control mice (Fig. 4). This infiltration was significantly suppressed by lovastatin treatment.

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