tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2010 Dec 10. [Epub ahead of print]
Pharmacologic Activation of the Innate Immune System to Prevent Respiratory Viral Infections.
Cheng G, Wang LC, Fridlender ZG, Cheng GS, Chen B, Mangalmurti NS, Saloura V, Yu Z, Kapoor V, Mozdzanowska K, Moon E, Sun J, Kreinder JL, Cohen NA, Caton AJ, Erikson J, Albelda SM.
Thoracic Oncology Research Laboratory, University of Pennsylvania, Philadelphia, United States.
Abstract
Drugs that can rapidly inhibit respiratory infection from influenza or other respiratory pathogens are needed. One approach is to take advantage of the primary innate immune defense against viral infection by directly activating the interferon pathway. In this study, we report a small, cell-permeable compound called 5,6-di-methylxanthenone-4-acetic acid (DMXAA), can induce protection against vesicular stomatitis virus (VSV) and H1N1 influenza A virus in vitro and in vivo through innate immune activation. Using the mouse C10 bronchial epithelial cell line and primary cultures of nasal epithelial cells, we demonstrate DMXAA activates the interferon regulatory factor-3 IRF3 pathway leading to production of IFN? and subsequent high level induction of IFN?-dependent proteins (such as Mx1 and OAS1). Mice treated with DMXAA intranasally elevate mRNA/protein expression of Mx1 and OAS1 in the nasal mucosa, trachea, and lung. When challenged intranasally with a lethal dose of H1N1 influenza A virus, DMXAA reduced viral titers in the lungs and protected 80% of mice from death, even when given at 24 hours prior to infection. These data show that agents, like DMXAA, that can directly activate the IRF3/IFN? system in respiratory epithelial cells can be used to protect from influenza pneumonia and potentially in other respiratory viral infections. Development of this approach in humans could be especially valuable for protecting health care professionals and "first responders" in the early stages of viral pandemics or bioterror attacks.
PMID: 21148741 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21148741
Pharmacologic Activation of the Innate Immune System to Prevent Respiratory Viral Infections.
Cheng G, Wang LC, Fridlender ZG, Cheng GS, Chen B, Mangalmurti NS, Saloura V, Yu Z, Kapoor V, Mozdzanowska K, Moon E, Sun J, Kreinder JL, Cohen NA, Caton AJ, Erikson J, Albelda SM.
Thoracic Oncology Research Laboratory, University of Pennsylvania, Philadelphia, United States.
Abstract
Drugs that can rapidly inhibit respiratory infection from influenza or other respiratory pathogens are needed. One approach is to take advantage of the primary innate immune defense against viral infection by directly activating the interferon pathway. In this study, we report a small, cell-permeable compound called 5,6-di-methylxanthenone-4-acetic acid (DMXAA), can induce protection against vesicular stomatitis virus (VSV) and H1N1 influenza A virus in vitro and in vivo through innate immune activation. Using the mouse C10 bronchial epithelial cell line and primary cultures of nasal epithelial cells, we demonstrate DMXAA activates the interferon regulatory factor-3 IRF3 pathway leading to production of IFN? and subsequent high level induction of IFN?-dependent proteins (such as Mx1 and OAS1). Mice treated with DMXAA intranasally elevate mRNA/protein expression of Mx1 and OAS1 in the nasal mucosa, trachea, and lung. When challenged intranasally with a lethal dose of H1N1 influenza A virus, DMXAA reduced viral titers in the lungs and protected 80% of mice from death, even when given at 24 hours prior to infection. These data show that agents, like DMXAA, that can directly activate the IRF3/IFN? system in respiratory epithelial cells can be used to protect from influenza pneumonia and potentially in other respiratory viral infections. Development of this approach in humans could be especially valuable for protecting health care professionals and "first responders" in the early stages of viral pandemics or bioterror attacks.
PMID: 21148741 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21148741