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- W4313385358 abstract "Abstract Mainstream and second hand cigarette smoke exposures increase the risk of respiratory viral infections, especially in children and those with underlying lung disease. Epithelial cells are the primary targets for viral infection and recognize foreign pathogens through multiple Toll-like receptors (TLR). TLR3 recognizes double stranded RNA, a common intermediate in virus replication, and activates antiviral signaling pathways. We hypothesized that cigarette smoke exposure impairs TLR3 signaling in airway epithelial cells leading to an increase in susceptibility to viral infection. Primary human small airway epithelial cells were cultured at the air-liquid interface and exposed to whole cigarette smoke. Following cigarette smoke exposure, cells were treated with the TLR3 ligand polyinosinic-polycytidylic acid (poly I:C), a mimic of RNA viral infection. Levels of interferon gamma induced protein 10 (IP-10) and antiviral interferon bioactivity were measured in culture supernatants. TLR3 cleavage was investigated using the cathepsin inhibitor z-FA-FMK and protein lysates were analyzed by western blot. Our data shows that cigarette smoke exposure causes a decrease in the production of IP-10, as well as a decrease in the interferon bioactivity of culture supernatants. Western blot data indicates that cigarette smoke inhibits cleavage of TLR3. Inhibitor studies confirmed that cleavage of TLR3 was important for the production of IP-10 and interferons. These data show that cigarette smoke disrupts the production of anti-viral signaling molecules by disrupting cleavage and activation of TLR3, as well as provides a mechanistic explanation for increased susceptibility to viral infections in smokers." @default.
- W4313385358 created "2023-01-06" @default.
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- W4313385358 date "2016-05-01" @default.
- W4313385358 modified "2023-10-12" @default.
- W4313385358 title "TLR3 signaling is impaired in small airway epithelial cells following cigarette smoke exposure." @default.
- W4313385358 doi "https://doi.org/10.4049/jimmunol.196.supp.203.14" @default.
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