Allergy Asthma Respir Dis.
2021 Apr;9(2):76-83. 10.4168/aard.2021.9.2.76.
Therapeutic effect of atorvastatin on interleukin-13-induced lung pathology
- Affiliations
-
- 1Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
- 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- 3Pulmonary, Critical Care and Sleep Medicine, Yale University, School of Medicine, New Haven, CT, USA
- 4Department of Molecular Microbiology and Immunology, Division of Biology and Medical Sciences, Brown University, Providence, RI, USA
- KMID: 2515254
- DOI: http://doi.org/10.4168/aard.2021.9.2.76
Abstract
- Purpose
Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on the IL-13-induced lung pathology through the modulation of macrophages.
Methods
Atorvastatin (40 mg/kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, numbers of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed.
Results
Significant reduction in total leukocytes and alleviation of AHR were observed with administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P< 0.05). Atorvastatin administration resulted in upregulation of IL-10 in the lungs of IL-13 TG mice (P< 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P< 0.05). M2 macrophage markers, such as Ym-1 and CD206, were decreased, while M1 macrophage marker, inducible nitric oxide synthase, was increased upon atorvastatin treatment (P< 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P< 0.05).
Conclusion
The results of this study reveal a potential of atorvastatin as an effective antiasthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Atorvastatin Induces FXR and CYP7A1 Activation as a Result of the Sequential Action of PPARγ/PGC-1α/HNF-4α in Hep3B Cells
- Therapeutic Effect of Adipose Derived Stem Cells versus Atorvastatin on Amiodarone Induced Lung Injury in Male Rat
- Atorvastatin inhibits the proliferation of MKN45-derived gastric cancer stem cells in a mevalonate pathway-independent manner
- Antiasthmatic effect of atorvastatin via modulation of macrophage activation
- IL-4/IL-13 Cytokine and Receptor in Asthma
