Document Detail


Toll-like receptor-2/6 and Toll-like receptor-9 agonists suppress viral replication but not airway hyperreactivity in guinea pigs.
MedLine Citation:
PMID:  23449736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Respiratory virus infections cause airway hyperreactivity (AHR). Preventative strategies for virus-induced AHR remain limited. Toll-like receptors (TLRs) have been suggested as a therapeutic target because of their central role in triggering antiviral immune responses. Previous studies showed that concurrent treatment with TLR2/6 and TLR9 agonists reduced lethality and the microbial burden in murine models of bacterial and viral pneumonia. This study investigated the effects of TLR2/6 and TLR9 agonist pretreatment on parainfluenza virus pneumonia and virus-induced AHR in guinea pigs in vivo. Synthetic TLR2/6 lipopeptide agonist Pam₂CSK₄ and Class C oligodeoxynucleotide TLR9 agonist ODN2395, administered in combination 24 hours before virus infection, significantly reduced viral replication in the lung. Despite a fivefold reduction in viral titers, concurrent TLR2/6 and TLR9 agonist pretreatment did not prevent virus-induced AHR or virus-induced inhibitory M2 muscarinic receptor dysfunction. Interestingly, the TLR agonists independently caused non-M2-dependent AHR. These data confirm the therapeutic antiviral potential of TLR agonists, while suggesting that virus inhibition may be insufficient to prevent virus-induced airway pathophysiology. Furthermore, TLR agonists independently cause AHR, albeit through a distinctly different mechanism from that of parainfluenza virus.
Authors:
Matthew G Drake; Scott E Evans; Burton F Dickey; Allison D Fryer; David B Jacoby
Related Documents :
23726196 - Virus inactivation on hard surfaces or in suspension by chemical disinfectants: systema...
23893826 - When rectal bleeding is serious: anal squamous cell carcinoma in two intravenous cyclop...
23394546 - Aleutian mink disease virus in furbearing mammals in nova scotia, canada.
24008376 - Ecology of west nile virus in north america.
21147926 - Comprehensive characterization of interaction complexes of herpes simplex virus type 1 ...
8179476 - Antineoplastic and antiviral activities of podophyllotoxin related lignans.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-04     Completed Date:  2013-08-05     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  790-6     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Antiviral Agents / pharmacology
Bronchial Hyperreactivity / immunology,  physiopathology,  virology*
Bronchoconstriction
Drug Synergism
Female
Guinea Pigs
Leukocyte Count
Lipopeptides / pharmacology
Lung / drug effects,  immunology,  virology
Oligodeoxyribonucleotides / pharmacology
Receptor, Muscarinic M3 / drug effects,  immunology
Respirovirus Infections / drug therapy,  immunology,  physiopathology,  virology
Sendai virus / immunology,  physiology
Specific Pathogen-Free Organisms
Toll-Like Receptor 2 / agonists*,  immunology
Toll-Like Receptor 6 / agonists*,  immunology
Toll-Like Receptor 9 / agonists*,  immunology
Virus Replication / drug effects*
Grant Support
ID/Acronym/Agency:
ES014601/ES/NIEHS NIH HHS; HL071795/HL/NHLBI NIH HHS; HL115903/HL/NHLBI NIH HHS; HL54659/HL/NHLBI NIH HHS; HL55543/HL/NHLBI NIH HHS; R01 HL113023/HL/NHLBI NIH HHS; T-32 HL-83808/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/CpG ODN 2395; 0/Lipopeptides; 0/Oligodeoxyribonucleotides; 0/Pam2CSK4 lipopeptide; 0/Receptor, Muscarinic M3; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 6; 0/Toll-Like Receptor 9; N9YNS0M02X/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Human eosinophils express functional CCR7.
Next Document:  Effect of Asbestos Exposure on Differentiation of Cytotoxic T Lymphocytes in MLR of Human PBMCs.