title: C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression.
abstract: Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide. Transepithelial resistance (TER) was measured to assess the epithelial cell permeability. Western blotting and real-time quantitative polymerase chain reaction were used to detect the mRNA and protein levels of tight junction, respectively. After incubation with different concentrations of c2-ceramide, TER of AECII monolayer decreased significantly in a dose-dependent manner. Moreover, expressions of ZO-1, occludin and claudin-4 were significantly reduced by c2-ceramide in the study. This study demonstrated that ceramide could increase alveolar epithelial cell monolayer permeability by downregulation of tight junction proteins. Therefore, modulation of ceramide expression may serve as a new therapeutic approach to treat acute lung injury.
authors.affiliation: a Department of Respiratory Medicine , the Second Hospital of Anhui Medical University , Hefei , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: b Department of Respiratory Medicine , the People's Hospital of Lu'an City , Lu'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Respiratory Medicine , the Second Hospital of Anhui Medical University , Hefei , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Department of Respiratory Medicine , the Second Hospital of Anhui Medical University , Hefei , China.
authors.forename: Jirui
authors.initials: J
authors.lastname: Bi
authors.affiliation: a Department of Respiratory Medicine , the Second Hospital of Anhui Medical University , Hefei , China.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D062506:Claudin-4 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D051379:Mice; D008813:Mice, Inbred ICR; D062793:Occludin / Q000235:genetics*; D010539:Permeability; D061251:Primary Cell Culture; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000235:genetics*
chemical_list: D062506:Claudin-4; C568158:Cldn4 protein, mouse; C064769:N-acetylsphingosine; D062793:Occludin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D013110:Sphingosine
keywords: Ceramide; acute lung injury; epithelial permeability; lung edema; tight junctions