Gene Expression Profiles Underlying Selective T-Cell-Mediated Immunity Activity of a Chinese Medicine Granule on Mice Infected with Influenza Virus H1N1
A Chinese medicine granule, Shu-Feng-Xuan-Fei (SFXF), is critical for viral clearance in early phase of influenza virus infection. In this study, 72 ICR mice were randomly divided into six groups: normal control group, virus control group, Oseltamivir group, low-dose SFXF, medium-dose SFXF, and high-dose SFXF. Mice were anesthetized and inoculated with 4LD50 of influenza virus A (H1N1) except normal control group. Oseltamivir group received 11.375 mg·kg？1·d？1 Oseltamivir Phosphate. SFXF 3.76, 1.88 and 0.94 g·kg？1·d？1 were administrated to mice in all SFXF groups. Each group was in equal dose of 0.2ml daily for 4 consecutive days. Mice were sacrificed and then total RNA was extracted in lung tissue. Some genes involved in T-cell-mediated immunity were selected by DNA microarray. These candidate genes were verified by Real-Time PCR and western immunoblotting. Compared with virus control group, in Toll-like receptor signaling pathway, 12 virus-altered genes were significantly reduced following medium-dose SFXF treatment. Eighteen antigen processing presentation-associated genes were upregulated by medium-dose SFXF. In the process of T cell receptor signaling pathway, 19 genes were downregulated by medium-dose SFXF treatment. On exploration into effector T cells activation and cytokines, all of altered genes in virus control group were reversed by medium-dose SFXF. Real-time PCR and western immunoblotting showed that the regulation of medium-dose SFXF in IL-4, IFN- , TNF- , IL-1 , TLR7, MyD88, p38, and JNK was superior to Oseltamivir and high-dose SFXF group. Therefore, SFXF granules could reduce influenza infected cells and activation of T cells. 1. Introduction Influenza virus A (H1N1) has emerged every year and remained a public health threat worldwide. Influenza virus not only can damage the epithelial cells, of the lung and airways, but also may lead to complications of extrarespiratory diseases. Today the main option for prevention and treatment is the neuraminidase inhibitor (NAI), Oseltamivir Phosphate, which prolongs influenza virus shedding, decreases the signs of infection, reduces the spread of H1N1pdm influenza virus in the lungs of ferrets, and impedes the development of viral pneumonia [1]. However, the risk of Oseltamivir for virus strain resistance, possible side effects, and financial cost outweigh the small benefits for the prophylaxis and treatment of healthy individuals [2]. To address these issues, other effective alternative treatments of symptomatic influenza, especially Chinese herbal granules, will be additionally needed to have
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