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Alcohol‐induced tight junction dysfunction primes airways for RSV infection (538.1)
Author(s) -
Simet Samantha,
Wyatt Todd,
Pavlik Jacqueline,
Sisson Joseph
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.538.1
Subject(s) - tight junction , alcohol , leak , immunology , permeability (electromagnetism) , lung , airway , medicine , microbiology and biotechnology , biology , chemistry , anesthesia , biochemistry , environmental engineering , membrane , engineering
Tight junctions form a belt‐like structure between adjacent cells whose degree of permeability changes according to external stimuli, physiological and pathological conditions. We have previously shown that alcohol increases tight junction permeability and disrupts tight junction proteins (ZO‐1 and claudin) in cultured airway epithelial cells through PKCα. It is well established that individuals who consume heavy and prolonged amounts of alcohol are more likely to suffer from pulmonary diseases and infections. Alcohol triggers tight junctions in airway epithelial cells to “leak”, which likely primes the airways for pulmonary infections. Thus, a second injury, such as viral or bacterial infection, is likely intensified by alcohol consumption. To date, very few studies have focused on the combination of alcohol and RSV infection. While both alcohol and RSV have been separately shown to disrupt tight junctions, little research has examined the combination of alcohol and RSV infection on tight junction function. We hypothesize that alcohol primes the airways for RSV infection and exacerbates RSV infection significantly increasing tight junction permeability and airway epithelial injury. Preliminary cell culture data demonstrates that Gö6976, a PKCαinhibitor, and Y27632, a Rho‐associated protein kinase (ROCK) inhibitor, prevent alcohol‐induced tight junction “leak”. In addition, the combination of alcohol exposure and RSV infection increase tight junction permeability considerably more than RSV or alcohol alone. Together our preliminary data suggest that alcohol‐induced tight junction disruption primes the airways for RSV infection. Grant Funding Source : Supported by I01BX000728 (TAW) and R01AA008769 (JHS)