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IL‐1β Induces Brain Microvascular Endothelial Cell Hyperpemeability Through Caspase‐3
Author(s) -
Wilson Rickesha L,
Sawant Devendra A,
Stagg Hayden W,
Davis Matthew L,
Smythe W. Roy,
Tharakan Binu
Publication year - 2012
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.26.1_supplement.lb695
Subject(s) - occludin , tight junction , proinflammatory cytokine , neuroinflammation , endothelial stem cell , microbiology and biotechnology , adherens junction , blood–brain barrier , chemistry , caspase 1 , caspase 3 , phalloidin , inflammation , apoptosis , medicine , cell , biology , immunology , programmed cell death , cytoskeleton , biochemistry , central nervous system , cadherin , in vitro
Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality worldwide. TBI is associated with brain edema, neuroinflammation and upregulation of proinflammatory cytokines. Interleukin‐1β (IL‐1β) is a major cytokine implicated in the adverse consequences of TBI. We hypothesized that IL‐1β induces brain microvascular hyperpermeability and edema via caspase‐3 mediated barrier dysfunction. Our prior studies have demonstrated caspase‐3 to be a key mediator in cell junction disruption. Rat brain microvascular endothelial cells were exposed to IL ‐ 1β following caspase‐3 inhibitor Z‐DEVD (10μM) pretreatment. The permeability was determined using FITC‐dextran flux across the Transwell monolayer. Caspase‐3 activity was measured fluorometrically. The endothelial cell tight junction integrity was studied by immunofluorescence of zonula occludens‐1, claudin‐5 and occludin. The f ‐actin stress fiber formation was studied using rhodamine phalloidin staining. Z‐DEVD attenuated IL ‐ 1β‐induced hyperpermeability significantly ( p <0.05). IL ‐ 1β induced caspase‐3 activity significantly ( p <0.05). Z‐DEVD decreased IL ‐ 1β induced disruption of the tight junctions and f‐ actin stress fiber formation. IL ‐ 1β induces disruption of the brain endothelial cell barrier leading to hyperpermeability through caspase‐3‐mediated cleavage of the tight junction proteins.