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Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model.
Eur J Pharmacol. 2007 Feb 14; 557(1):76-86.EJ

Abstract

Statins have anti-inflammatory property and immunomodulatory activity. In this study we aimed to investigate the inhibitory mechanism of simvastatin in allergic asthmatic symptoms in mice. BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. Ovalbumin-specific serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA), and the recruitment of inflammatory cells into bronchoalveolar lavage fluid or lung tissues was measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining, respectively, the expressions of CD40, CD40 ligand (CD40L), and vascular cell adhesion molecule-1 (VCAM-1) by immunohistochemistry, the mRNA and protein expressions of cytokines in lung tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) or ELISA, epithelial hyperplasia by periodic acid-Schiff (PAS) staining, activities of matrix metalloproteinases (MMPs) by zymography, the activities of small G proteins, mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-kappaB) in bronchoalveolar lavage cells and lung tissues by western blot and EMSA, respectively. Simvastatin reduced ovalbumin-specific IgE level, the number of total inflammatory cells, macrophages, neutrophils, and eosinophils into bronchoalveolar lavage fluid, the expressions of CD40, CD40L or VCAM-1, the mRNA and protein levels of interleukin (IL)-4, IL-13 and tumor necrosis factor (TNF)-alpha, the numbers of goblet cells, activities of MMPs, and further small G proteins, MAP kinases and NF-kappaB activities in bronchoalveolar lavage cells and lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that simvastatin may be used as a therapeutic agent in asthma, based on reductions of various allergic responses via regulating small G proteins/MAP kinases/NF-kappaB in mouse allergic asthma.

Authors+Show Affiliations

Department of Pharmacology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17169357

Citation

Kim, Dae Yong, et al. "Anti-inflammatory Mechanism of Simvastatin in Mouse Allergic Asthma Model." European Journal of Pharmacology, vol. 557, no. 1, 2007, pp. 76-86.
Kim DY, Ryu SY, Lim JE, et al. Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. Eur J Pharmacol. 2007;557(1):76-86.
Kim, D. Y., Ryu, S. Y., Lim, J. E., Lee, Y. S., & Ro, J. Y. (2007). Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. European Journal of Pharmacology, 557(1), 76-86.
Kim DY, et al. Anti-inflammatory Mechanism of Simvastatin in Mouse Allergic Asthma Model. Eur J Pharmacol. 2007 Feb 14;557(1):76-86. PubMed PMID: 17169357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model. AU - Kim,Dae Yong, AU - Ryu,Su Youn, AU - Lim,Ji Eun, AU - Lee,Yun Song, AU - Ro,Jai Youl, Y1 - 2006/11/15/ PY - 2006/08/02/received PY - 2006/10/28/revised PY - 2006/11/01/accepted PY - 2006/12/16/pubmed PY - 2007/4/14/medline PY - 2006/12/16/entrez SP - 76 EP - 86 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 557 IS - 1 N2 - Statins have anti-inflammatory property and immunomodulatory activity. In this study we aimed to investigate the inhibitory mechanism of simvastatin in allergic asthmatic symptoms in mice. BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. Ovalbumin-specific serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA), and the recruitment of inflammatory cells into bronchoalveolar lavage fluid or lung tissues was measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining, respectively, the expressions of CD40, CD40 ligand (CD40L), and vascular cell adhesion molecule-1 (VCAM-1) by immunohistochemistry, the mRNA and protein expressions of cytokines in lung tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) or ELISA, epithelial hyperplasia by periodic acid-Schiff (PAS) staining, activities of matrix metalloproteinases (MMPs) by zymography, the activities of small G proteins, mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-kappaB) in bronchoalveolar lavage cells and lung tissues by western blot and EMSA, respectively. Simvastatin reduced ovalbumin-specific IgE level, the number of total inflammatory cells, macrophages, neutrophils, and eosinophils into bronchoalveolar lavage fluid, the expressions of CD40, CD40L or VCAM-1, the mRNA and protein levels of interleukin (IL)-4, IL-13 and tumor necrosis factor (TNF)-alpha, the numbers of goblet cells, activities of MMPs, and further small G proteins, MAP kinases and NF-kappaB activities in bronchoalveolar lavage cells and lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that simvastatin may be used as a therapeutic agent in asthma, based on reductions of various allergic responses via regulating small G proteins/MAP kinases/NF-kappaB in mouse allergic asthma. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17169357/Anti_inflammatory_mechanism_of_simvastatin_in_mouse_allergic_asthma_model_ DB - PRIME DP - Unbound Medicine ER -