Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model.
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.
Kim
Dae Yong
DY
Department of Pharmacology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.
Ryu
Su Youn
SY
Lim
Ji Eun
JE
Lee
Yun Song
YS
Ro
Jai Youl
JY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007958:Leukocyte Count; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand; D007073:Immunoglobulin E; D010047:Ovalbumin; D019821:Simvastatin; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; D019204:GTP-Binding Proteins