Microtubule stabilization opposes the (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium.
Microtubule disassembly breaks down the barrier integrity in a number of epithelial and endothelial monolayers. This study has investigated effects of TNF-alpha, which is implicated in corneal allograft rejection, on microtubules and barrier integrity in cultured bovine corneal endothelial cells. Exposure to TNF-alpha led to disassembly of the microtubules, and also caused disruption of the perijunctional actomyosin ring (PAMR). As a measure of barrier integrity, trans-endothelial electrical resistance (TER) was determined based on electrical cell-substrate impedance sensing in realtime. Exposure to TNF-alpha caused a slow decline in TER for > 20 h, and a similar exposure to cells grown on porous culture inserts led to a significant increase in permeability to FITC dextran. These changes, indicating a loss of barrier integrity, were also reflected by dislocation of ZO-1 at the cell border and disassembly of cadherins. These effects of TNF-alpha were inhibited upon stabilization of microtubules by pre-treatment with paclitaxel or epothilone B. Microtubule stabilization may be a useful strategy to overcome (TNF-alpha)-induced loss of the barrier integrity of corneal endothelium during inflammation associated with transplant rejection and uveitis.
Shivanna
Mahesh
M
School of Optometry, 800 E. Atwater Avenue, Indiana University, Bloomington, IN 47405, USA.
Srinivas
Sangly P
SP
D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003911:Dextrans / Q000493:pharmacokinetics; D017097:Electric Impedance; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D034261:Epothilones / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D015820:Cadherins; D003911:Dextrans; D034261:Epothilones; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D050257:Tubulin Modulators; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel; C093788:epothilone B
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