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Interleukin‐1β induces brain microvascular endothelial cell hyperpermeability through matrix metalloproteinase‐9 (678.17)
Author(s) -
Alluri Himakarnika,
Anasooya Shaji Chinchusha,
WigginsDohlvik Katie,
Oakley Ryan,
Stagg Hayden,
Davis Matthew,
Tharakan Binu
Publication year - 2014
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.28.1_supplement.678.17
Subject(s) - blood–brain barrier , tight junction , matrix metalloproteinase , chemistry , occludin , evans blue , phalloidin , microbiology and biotechnology , endothelial stem cell , cytoskeleton , cell , biology , endocrinology , biochemistry , in vitro , central nervous system
Interleukin‐1β induces Brain Microvascular Endothelial Cell Hyperpermeability through Matrix metalloproteinase‐9 Himakarnika Alluri, Chinchusha Anasooya Shaji, Katie Wiggins‐Dohlvik, Ryan Oakley, Hayden W. Stagg, Matthew L. Davis, Binu Tharakan. Surgery, Texas A&M University Health Science Center & Baylor Scott and White Health, Temple, TX, USA. Brain microvascular hyperpermeability is a major contributor of vasogenic brain edema that occurs following traumatic and ischemic injuries and involves upregulation of interleukin‐1 beta (IL‐1β). Our objective was to determine if IL‐1β mediates blood‐brain barrier (BBB) hyperpermeability via Matrix Metalloproteinases (MMPs)‐induced tight junction (TJ) disruption. Rat brain microvascular endothelial cell (RBMEC) monolayers were exposed to various concentrations of IL‐1β and the optimal concentration and time to induce permeability were determined. RBMEC monolayers were exposed to IL‐1β alone or following an MMP inhibitor (GM6001; 1hour) and MMP‐9 siRNA. MMP‐9 activity was measured following IL‐1β exposure. TJ integrity and cytoskeletal assembly were studied using zonula occludens‐1 (ZO‐1) immunofluorescence and rhodamine phalloidin staining for f ‐actin respectively. IL‐1β increased monolayer permeability and MMP‐9 activity significantly (p<0.05) and induced TJ disruption and actin stress fiber formation. GM6001 and MMP‐9 siRNA attenuated IL‐1β‐induced hyperpermeability significantly ( p <0.05). An MMP‐9 specific inhibitor (MMP inhibitor‐1) protected both TJ integrity and actin cytoskeletal assembly. These findings suggest that up‐regulation of IL‐1β promotes activation of MMP‐9 leading to BBB breakdown and microvascular hyperpermeability.