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Alcohol‐induced alterations of alveolar macrophage transforming growth factor beta 1 (TGFβ1) levels decrease epithelial barrier function
Author(s) -
CurryMcCoy Tiana V,
Guidot David M,
Joshi Pratibha C
Publication year - 2011
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.25.1_supplement.1066.2
Subject(s) - paracellular transport , transforming growth factor , barrier function , epithelium , chemistry , transforming growth factor beta , alveolar macrophage , microbiology and biotechnology , macrophage , medicine , lung , endocrinology , biology , pathology , permeability (electromagnetism) , biochemistry , in vitro , membrane
TGFβ1 participates in normal lung development, epithelial cell maturation, and the proliferation and differentiation of alveolar macrophages (AM). Prolonged and/or excessive TGFβ1 expression can lead to acute lung injury. We hypothesized that exposure to alcohol increases AM TGFβ1 production and release, which in turn causes disruption of alveolar epithelial barrier function. We used the rat AM and lung epithelial cell lines (NR8383 and LT cells, respectively) or primary rat alveolar epithelial cells to test our hypothesis. Primary lung epithelial and L2 cells were treated ± alcohol or TGFβ1; in other experiments cell lysates from alcohol treated AM were added to cultured epithelial cells. Changes in paracellular permeability were examined by measuring the transepithelial resistance (TER) and the paracellular flux of Texas Red dye. Treatment of epithelial cells with alcohol, TGFβ1, or lysate from alcohol‐treated AM decreased the TER and increased flux of dye as compared with controls. In addition, treatment of alcohol‐primed cells with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) increased TER. These results suggest that alcohol increases TGFβ1 production in AM, which in turn can disrupt the normally tight paracellular barrier in the alveolar epithelium. Interestingly, it appears that these alcohol‐induced effects of TGFβ1 can be reversed with GM‐CSF. Supported by NIH/NIAAA