title: Interleukin-17F-induced pulmonary microvascular endothelial monolayer hyperpermeability via the protein kinase C pathway.
abstract: BACKGROUND
  Interleukin (IL)-17F is involved in lung inflammation, but the effect of IL-17F on endothelial permeability and its signaling pathway remain ill-defined. The current study sought to investigate the effect of IL-17F on endothelium and assess the role of protein kinase C (PKC) and src-suppressed C kinase substrate (SSeCKS) in this process.
  
  
  METHODS
  Rat pulmonary microvascular endothelial monolayers were constructed to determine changes of permeability as measured by means of FITC-dextran and Hank's solution flux across monolayers and transendothelial electrical resistance with or without IL-17F and PKC inhibitors. Additional monolayers were stained using FITC-phalloidin for filamentous actin (F-actin). The gene expression of SSeCKS was analyzed by the reverse transcription-polymerase chains. Alterations of SSeCKS protein were investigated by immunoblotting and immunoprecipitation.
  
  
  RESULTS
  IL-17F increased endothelial monolayer permeability in a dose- and time-dependent manner. F-actin staining revealed that permeability changes were accompanied by reorganization of cytoskeleton. In the presence of PKC inhibitors, the IL-17F-induced hyperpermeability and reorganization of F-actin were attenuated. The gene and protein expression of SSeCKS were conspicuously elevated after IL-17F challenge. The process of SSeCKS phosphorylation followed a time course that mirrored the time course of hyperpermeability induced by IL-17F. IL-17F-induced SSeCKS phosphorylation was abrogated after PKC inhibitors pretreatment. The translocation of SSeCKS from the cytosol to the membrane and a significant increase in the SSeCKS association with the cytoskeleton were found after IL-17F treatment.
  
  
  CONCLUSIONS
  IL-17F is an important mediator of increased endothelial permeability. PKC and SSeCKS are integral signaling components essential for IL-17F-induced hyperpermeability.
authors: Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China.
authors: Qing-hai
authors: QH
authors: You
authors: Geng-yun
authors: GY
authors: Sun
authors: Nan
authors: N
authors: Wang
authors: Ji-long
authors: JL
authors: Shen
authors: Yuan
authors: Y
authors: Wang
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000098:blood supply; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; D000199:Actins; C102361:Akap12 protein, rat; D018797:Cell Cycle Proteins; D020381:Interleukin-17; D011493:Protein Kinase C