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<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">JMDS</journal-id><journal-title-group><journal-title>Journal of Medicines Development Sciences</journal-title></journal-title-group><issn>2382-6363</issn><eissn>2382-6371</eissn><publisher><publisher-name>WHIOCE PUBLISHING PTE. LTD.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18063/jmds.v8i1.142</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Therapeutic Effect of Atorvastatin on Interleukin-13- Induced Lung Pathology</title><url>https://artdesignp.com/journal/JMDS/8/1/10.18063/jmds.v8i1.142</url><author>MoYosep,BaeBoram,KimJunghyun,KimRuth Lee,SonKyunghee,KangMin-Jong,LeeChun-Gen,ChoSang-Heon,KangHye-Ryun</author><pub-date pub-type="publication-year"><year>2023</year></pub-date><volume>8</volume><issue>1</issue><history><date date-type="pub"><published-time>2023-08-25</published-time></date></history><abstract>PPurpose:&amp;nbsp;Asthma is a common chronic lung disease, in which interleukin (IL)-13&amp;nbsp;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 IL-13-induced&amp;nbsp;lung pathology through the modulation of macrophages.&amp;nbsp;Methods:&amp;nbsp;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, the number of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar&amp;nbsp;macrophage (AM) cell line CRL-2456, the direct effect of atorvastatin on macrophages&amp;nbsp;activated by recombinant IL-13 was assessed.&amp;nbsp;Results:&amp;nbsp;Significant reduction in total&amp;nbsp;leukocytes and alleviation of AHR were observed with the administration of atorvastatin in&amp;nbsp;IL-13 TG mice compared to those without atorvastatin treatment (P&amp;nbsp;&amp;lt; 0.05). Atorvastatin&amp;nbsp;administration resulted in the upregulation of IL-10 in the lungs of IL-13 TG mice (P&amp;nbsp;&amp;lt;&amp;nbsp;0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and&amp;nbsp;type III collagen as well as chord length enhanced by IL-13 overexpression were reduced&amp;nbsp;by atorvastatin administration (P&amp;nbsp;&amp;lt; 0.05). M2 macrophage markers were decreased,&amp;nbsp;while the M1 macrophage marker was increased upon atorvastatin treatment (P&amp;nbsp;&amp;lt; 0.05).&amp;nbsp;Administration of atorvastatin resulted in improved removal of apoptotic cells (P&amp;nbsp;&amp;lt; 0.05).&amp;nbsp;Conclusion:&amp;nbsp;The results of this study reveal the potential of atorvastatin as an effective anti-asthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.</abstract><keywords>Asthma, Interleukin-13, Atorvastatin, Anti-asthmatic agents, Macrophage</keywords></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Wills-Karp M, 1999, Immunologic Basis of Antigen-Induced Airway Hyperresponsiveness. Annu Rev Immunol, 17:
&amp;ndash;281.
Cohn L, Elias JA, Chupp GL, 2004, Asthma: Mechanisms of Disease Persistence and Progression. Annu Rev
Immunol, 22: 789-815.
Wills-Karp M, 2004, Interleukin-13 in Asthma Pathogenesis. Curr Allergy Asthma Rep, 4(2): 123&amp;ndash;131.
Zhu Z, Homer RJ, Wang Z, et al, 1999, Pulmonary Expression of Interleukin-13 Causes Inflammation, Mucus
Hypersecretion, Subepithelial Fibrosis, Physiologic Abnormalities, and Eotaxin Production. J Clin Invest, 103(6):
&amp;ndash;788.
Byrne AJ, Mathie SA, Gregory LG, et al, 2015, Pulmonary Macrophages: Key Players in the Innate Defence of the
Airways. Thorax, 70(12): 1189&amp;ndash;1196.
Murray PJ, 2017, Macrophage Polarization. Annu Rev Physiol, 79: 541&amp;ndash;566.
Arango Duque G, Descoteaux A, 2014, Macrophage Cytokines: Involvement in Immunity and Infectious Diseases.
Front Immunol, 5: 491.
van der Veen TA, de Groot LES, Melgert BN, 2020, The Different Faces of the Macrophage in Asthma. Curr Opin
Pulm Med, 26(1): 62&amp;ndash;68.
Abdelaziz MH, Abdelwahab SF, Wan J, et al, 2020, Alternatively Activated Macrophages; A Double-Edged Sword in
Allergic Asthma. J Transl Med, 18(1): 58.
Fricker M, Gibson PG, 2017, Macrophage Dysfunction in the Pathogenesis and Treatment of Asthma. Eur Respir J,
(3): 1700196.
Haque T, Khan BV, 2020, Atorvastatin: A Review of Its Pharmacological Properties and Use in Familial
Hypercholesterolemia. Clin Lipidol, 5: 615&amp;ndash;625.
Inagaki-Katashiba N, Ito T, Inaba M, et al, 2019, Statins Can Suppress DC-Mediated Th2 Responses Through the
Repression of OX40-Ligand and CCL17 Expression. Eur J Immunol, 49(11): 2051&amp;ndash;2062.
Mausner-Fainberg K, Luboshits G, Mor A, et al, 2008, The Effect of HMG-CoA Reductase Inhibitors on Naturally
Occurring CD4+CD25+ T Cells. Atherosclerosis, 197(2): 829&amp;ndash;839.
Kang H-R, Lee CG, Homer RJ, et al, 2007, Semaphorin 7A Plays a Critical Role in TGF-Beta1-Induced Pulmonary
Fibrosis. J Exp Med, 204(5): 1083&amp;ndash;1093.
Morimoto K, Janssen WJ, Terada M, 2012, Defective Efferocytosis by Alveolar Macrophages in IPF Patients. Respir
Med, 106(12): 1800&amp;ndash;1803.
Sutherland ER, Martin RJ, 2003, Airway Inflammation in Chronic Obstructive Pulmonary Disease: Comparisons
with Asthma. J Allergy Clin Immunol, 112(5): 819&amp;ndash;827; Quiz 828.
Wynn TA, Chawla A, Pollard JW, 2013, Macrophage Biology in Development, Homeostasis and Disease. Nature,
(7446): 445&amp;ndash;455.
Saradna A, Do DC, Kumar S, et al, 2018, Macrophage Polarization and Allergic Asthma. Transl Res, 191: 1&amp;ndash;14.
Girodet PO, Nguyen D, Mancini JD, et al, 2016, Alternative Macrophage Activation is Increased in Asthma. Am J
Respir Cell Mol Biol, 55(4): 467&amp;ndash;475.
Lee HS, Kwon H-S, Park D-E, et al, 2015, Thalidomide Inhibits Alternative Activation of Macrophages In Vivo and
In Vitro: A Potential Mechanism of Anti-Asthmatic Effect of Thalidomide. PLoS One, 10(4): e0123094.
Shim JS, Lee H-S, Park D-E, et al, 2020, Aggravation of Asthmatic Inflammation by Chlorine Exposure via Innate
Lymphoid Cells and CD11cintermediate Macrophages. Allergy, 75(2): 381&amp;ndash;391.
Kim J, Chang Y, Bae B, et al, 2019, Innate Immune Crosstalk in Asthmatic Airways: Innate Lymphoid Cells
Coordinate Polarization of Lung Macrophages. J Allergy Clin Immunol, 143(5): 1769&amp;ndash;1782.e11.
Kasaian MT, Marquette K, Fish S, et al, 2013, An IL-4/IL-13 Dual Antagonist Reduces Lung Inflammation, Airway
Hyperresponsiveness, and IgE Production in Mice. Am J Respir Cell Mol Biol, 49(1): 37&amp;ndash;46.
Luo J, Liu D, Liu C-T, 2016, The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients
With Asthma: A Systematic Review and Meta-Analysis. Medicine (Baltimore), 95(6): e2556.
Li H, Wang K, Huang H, et al, 2019, A Meta-Analysis of Anti-Interleukin-13 Monoclonal Antibodies for
Uncontrolled Asthma. PLoS One, 14(1): e0211790.
Liou C-J, Cheng P-Y, Huang W-C, et al, 2014, Oral Lovastatin Attenuates Airway Inflammation and Mucus Secretion
in Ovalbumin-Induced Murine Model of Asthma. Allergy Asthma Immunol Res, 6(6): 548&amp;ndash;557.
Gu W, Cui R, Ding T, et al, 2017, Simvastatin Alleviates Airway Inflammation and Remodelling Through UpRegulation of Autophagy in Mouse Models of Asthma. Respirology, 22(3): 533&amp;ndash;541.
Braganza G, Chaudhuri R, McSharry C, et al, 2011, Effects of Short-Term Treatment With Atorvastatin in Smokers
With Asthma - A Randomized Controlled Trial. BMC Pulm Med, 11: 16.
Yuan C, Zhou L, Cheng J, et al, 2012, Statins as Potential Therapeutic Drug for Asthma? Respir Res, 13: 108.
Maneechotesuwan K, Ekjiratrakul W, Kasetsinsombat K, et al, 2010, Statins Enhance the Anti-Inflammatory Effects
of Inhaled Corticosteroids in Asthmatic Patients Through Increased Induction of Indoleamine 2, 3-Dioxygenase. J
Allergy Clin Immunol, 126(4): 754&amp;ndash;762.e1.
Liu J-N, Suh D-H, Yang E-M, et al, 2014, Attenuation of Airway Inflammation by Simvastatin and the Implications
for Asthma Treatment: Is the Jury Still Out? Exp Mol Med, 46(9): e113.
McKay A, Leung BP, McInnes IB, et al, 2004, A Novel Anti-Inflammatory Role of Simvastatin in a Murine Model of
Allergic Asthma. J Immunol, 172(5): 2903&amp;ndash;2908.
Tulek B, Kiyan E, Kiyici A, et al, 2012, Effects of Simvastatin on Bleomycin-Induced Pulmonary Fibrosis in Female
Rats. Biol Res, 45(4): 345&amp;ndash;350.
Fu H, Alabdullah M, Grossmann J, et al, 2019, The Differential Statin Effect on Cytokine Production of Monocytes
or Macrophages is Mediated by Differential Geranylgeranylation-Dependent Rac1 Activation. Cell Death Dis,
(12): 880.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
