Premium
Role of YKL‐40 (chitinase 3‐like 1) in SIV/HIV encephalitis
Author(s) -
BonnehBarkay Dafna,
Wang Guoji,
Wiley Clayton A
Publication year - 2007
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.21.5.a404-a
Subject(s) - astrocytosis , microglia , neurodegeneration , inflammation , chemokine , biology , immunology , neuroinflammation , secretion , extracellular matrix , basic fibroblast growth factor , microbiology and biotechnology , growth factor , disease , medicine , pathology , immunohistochemistry , receptor , biochemistry
AIDS patients with dementia demonstrate HIV encephalitis (HIVE) with neuropathological changes that include activated and infected macrophages, astrocytosis and neurodegeneration. Proteomic analysis of brain and CSF from the SIV primate model has demonstrated specific increase in YKL‐40. YKL‐40 is highly expressed in acute and chronic inflammatory conditions and is presumed to play a role in tissue remodeling processes and inflammation. We examined CSF concentration of YKL40 during HIV and SIV infection and found increased levels of YKL‐40. In vitro studies demonstrated YKL‐40 secretion by macrophages and microglia but not neurons or astrocytes. Surprisingly, in vivo YKL‐40 was associated with astrocytes in the vicinity of microglial nodules in SIVE cases. We found that while YKL40 was able to displace extracellular matrix bound basic Fibroblast Growth Factor (bFGF), it did not induce cytoxicity in mouse cortical neuron cultures. Taken together these findings demonstrate that YKL‐40 expressed during inflammation may regulate the biological activity of bFGF and potentially other heparin‐binding growth factors and chemokines that can affect neuronal survival.