Shenghai Huang1, Wei Wei, Yun Yun. 1. Department of Microbiology, 2 Institute of Clinical Pharmacology, Key Laboratory of Antiinflammatory and Immunopharmacology in Anhui Province, Anhui Medical University, Hefei 230032, China. shhuang@ahmu.edu.cn
Abstract
OBJECTIVE: TLR7 and TLR3 (Toll-like receptor, TLR) are important pattern recognition receptors (PRRs) that recognize the single-strand RNA and double-strand RNA of virus-origin. Respiratory syncytial virus (RSV) could be recognized by both TLR7 and TLR3. We studied the kinetics and profile of lung TLR7 and TLR3 expression during the early phase of the RSV infection, and explored their expression correlation with pulmonary inflammatory response. METHODS: We intranasally inoculated BALB/c mice with live RSV to induce acute lung inflammation,and detected the lung expression of TLR7 and TLR3 mRNA by semiquantitative RT-PCR analysis at day 1 after RSV infection. We also measured the transcription factor nuclear factor-kappaB (NF-kappaB) protein expression with western blot assay in nuclear extracts. Lung tissue sections were stained with hematoxylin and eosin, and examined under a light microscope for histopathological examination. RESULTS: SV infection could rapidly upregulate the lung expression levels of both TLR7 and TLR3 gene in a time-dependent manner. Furthermore, the response of TLR7 to RSV (1 h) was prior to that of TLR3 (4 h). It resulted in activation of NF-kappaB as soon as 4 h later in lung tissue. Moreover, RSV mediated early transcriptional responses of TLR7 and TLR3 were paralleling with the severe extent of RSV-induced pulmonary inflammation. CONCLUSION: TLR7 and TLR3 were really involved in RSV-induced lung inflammation by detecting the viral RNA. This may allow to detect viral infections and initiate a proinflammatory response via multiple TLRs. This study may be useful in the development of tools to modulate the activities of therapeutic TLR ligands.
OBJECTIVE:TLR7 and TLR3 (Toll-like receptor, TLR) are important pattern recognition receptors (PRRs) that recognize the single-strand RNA and double-strand RNA of virus-origin. Respiratory syncytial virus (RSV) could be recognized by both TLR7 and TLR3. We studied the kinetics and profile of lung TLR7 and TLR3 expression during the early phase of the RSV infection, and explored their expression correlation with pulmonary inflammatory response. METHODS: We intranasally inoculated BALB/c mice with live RSV to induce acute lung inflammation,and detected the lung expression of TLR7 and TLR3 mRNA by semiquantitative RT-PCR analysis at day 1 after RSV infection. We also measured the transcription factor nuclear factor-kappaB (NF-kappaB) protein expression with western blot assay in nuclear extracts. Lung tissue sections were stained with hematoxylin and eosin, and examined under a light microscope for histopathological examination. RESULTS:SV infection could rapidly upregulate the lung expression levels of both TLR7 and TLR3 gene in a time-dependent manner. Furthermore, the response of TLR7 to RSV (1 h) was prior to that of TLR3 (4 h). It resulted in activation of NF-kappaB as soon as 4 h later in lung tissue. Moreover, RSV mediated early transcriptional responses of TLR7 and TLR3 were paralleling with the severe extent of RSV-induced pulmonary inflammation. CONCLUSION:TLR7 and TLR3 were really involved in RSV-induced lung inflammation by detecting the viral RNA. This may allow to detect viral infections and initiate a proinflammatory response via multiple TLRs. This study may be useful in the development of tools to modulate the activities of therapeutic TLR ligands.
Authors: Sarah L Doyle; Kari Ann Shirey; Anne F McGettrick; Elaine F Kenny; Susan Carpenter; Brian E Caffrey; Siobhan Gargan; Susan R Quinn; Jorge H Caamaño; Paul Moynagh; Stefanie N Vogel; Luke A O'Neill Journal: J Biol Chem Date: 2013-07-19 Impact factor: 5.157
Authors: Susan Morris; Michele S Swanson; Andrew Lieberman; Michelle Reed; Zhenyu Yue; Dennis M Lindell; Nicholas W Lukacs Journal: J Immunol Date: 2011-09-12 Impact factor: 5.422