Premium
TWEAK stimulation of astrocytes and the proinflammatory consequences
Author(s) -
Saas Philippe,
Boucraut José,
Walker Paul R.,
Quiquerez AnneLise,
Billot Maryse,
DesplatJego Sophie,
Chicheportiche Yves,
Dietrich PierreYves
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/1098-1136(200010)32:1<102::aid-glia100>3.0.co;2-u
Subject(s) - proinflammatory cytokine , biology , astrocyte , tumor necrosis factor alpha , inflammation , microbiology and biotechnology , microglia , gliosis , neurodegeneration , neuroglia , receptor , neuroscience , immunology , central nervous system , medicine , pathology , biochemistry , disease
Astrocytes exert many active roles in brain homeostasis, potentially including the regulation of immune reactions. They possess a substantial aptitude for plasticity and, indeed, functional and phenotypic changes are frequently encountered in reactive gliosis observed in brain injuries. The significance of reactive astrocytes is still poorly defined, but it is clear that these cells are an important source of cytokines in inflamed brain. How tumor necrosis factor (TNF) and TNF‐receptor family members contribute to this reaction is an interesting issue that is currently being explored. It was previously shown that reactive astrocytes express high levels of Fas (CD95) and respond to Fas ligand (CD95L) by apoptosis or IL‐8 production. TWEAK (Apo‐3 ligand) is a recently identified member of the TNF family that is produced mainly by leukocytes that can infiltrate the inflamed brain and thus influence astrocyte behavior. Here we show that human astrocytes derived from different regions of the brain specifically bind TWEAK and are totally resistant to TWEAK mediated apoptosis. In addition, high amounts of IL‐8 and IL‐6 were secreted by astrocytes after TWEAK exposure. Finally, expression of cell surface molecules involved in the propagation and/or maintenance of brain inflammation was determined. TWEAK significantly increased ICAM‐1 expression on astrocytes, whereas no modification was detected in the expression of Fas, TNFRI, B7‐1, or MHC molecules. In conclusion, the proinflammatory effects induced by TWEAK on astrocytes in culture recapitulate many characteristics of reactive astrocytes observed in vivo, suggesting that TWEAK could play a significant role in brain inflammation. GLIA 32:102–107, 2000. © 2000 Wiley‐Liss, Inc.