Premium
Reprogramming of TIMP‐1 and TIMP‐3 expression profiles in brain microvascular endothelial cells and astrocytes in response to proinflammatory cytokines
Author(s) -
Bugno Marcin,
Witek Barbara,
Bereta Joanna,
Bereta Michal,
Edwards Dylan R.,
Kordula Tomasz
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00323-3
Subject(s) - proinflammatory cytokine , matrix metalloproteinase , microbiology and biotechnology , tumor necrosis factor alpha , cytokine , basement membrane , chemistry , inflammation , biology , immunology , biochemistry
Cytokine‐dependent regulation of tissue inhibitors of metalloproteinases (TIMPs) expression provides an important mechanism for controlling the activity of matrix metalloproteinases. We present data indicating that during inflammatory processes TIMP‐1 and TIMP‐3 may be involved in the proteolytic remodeling of subendothelial basement membrane of the brain microvascular system, a key step during leukocyte migration into the brain perivascular tissue. In brain endothelial cells the expression of TIMP‐1 is dramatically up‐regulated by major proinflammatory cytokines, with the combination of interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNFα) exhibiting the strongest synergistic stimulation. Simultaneously, IL‐1β/TNFα almost completely blocks TIMP‐3 expression. Both synergistic effects are dose‐dependent within the concentration range 0.05–5 ng/ml of both cytokines and correlate with the expression of inducible nitric oxide synthase, an endothelial cell activation marker. Down‐regulation of TIMP‐3 expression is also detected in astrocytes treated with TNFα or IFN‐γ, whereas oncostatin M as well as TNFα up‐regulate TIMP‐1 mRNA level. We propose that the cytokine‐modified balance between TIMP‐1 and TIMP‐3 expression provides a potential mechanism involved in the regulation of microvascular basement membrane proteolysis.