Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model.

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: Dae Yong Kim, Su Youn Ryu, Ji Eun Lim, Yun Song Lee, Jai Youl Ro
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 557 Issue 1 Pg. 76-86 (Feb 14 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17169357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• CD40 Antigens
• Cytokines
• NF-kappa B
• RNA, Messenger
• Vascular Cell Adhesion Molecule-1
• CD40 Ligand
• Immunoglobulin E
• Ovalbumin
• Simvastatin
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinases
• GTP-Binding Proteins

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Asthma (chemically induced, drug therapy, metabolism, pathology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• CD40 Antigens (metabolism)
• CD40 Ligand (metabolism)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Female
• GTP-Binding Proteins (metabolism)
• Immunoglobulin E (blood)
• Leukocyte Count
• Matrix Metalloproteinases (metabolism)
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Ovalbumin
• RNA, Messenger (metabolism)
• Simvastatin (pharmacology)
• Vascular Cell Adhesion Molecule-1 (metabolism)