TY - JOUR
T1 - Inflammatory cytokines and HIV-1-associated neurodegeneration
T2 - Oncostatin-M produced by mononuclear cells from HIV-1-infected individuals induces apoptosis of primary neurons
AU - Ensoli, Fabrizio
AU - Fiorelli, Valeria
AU - DeCristofaro, Maria
AU - Muratori, Donatella Santini
AU - Novi, Arianna
AU - Vannelli, Barbara
AU - Thiele, Carol J.
AU - Luzi, Giuseppe
AU - Aiuti, Fernando
PY - 1999/5/15
Y1 - 1999/5/15
N2 - Neurologic abnormalities are common in HIV-l-infected patients and often represent the dominant clinical manifestation of pediatric AIDS. The neurological dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macrophages and lymphocytes. By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individuals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postmitotic neuronal cells by inducing apoptotic cell death. Analysis of the cytokines produced by lymphomonocytic cells, HIV-1 infected or activated, indicated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-β1 concentrations were capable of enhancing oncM-mediated neuronal alterations, our data indicate that by acting in concert with other cytokines, oncM may induce neuronal demise in both the developing and the mature brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HIV-1-infected individuals.
AB - Neurologic abnormalities are common in HIV-l-infected patients and often represent the dominant clinical manifestation of pediatric AIDS. The neurological dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macrophages and lymphocytes. By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individuals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postmitotic neuronal cells by inducing apoptotic cell death. Analysis of the cytokines produced by lymphomonocytic cells, HIV-1 infected or activated, indicated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-β1 concentrations were capable of enhancing oncM-mediated neuronal alterations, our data indicate that by acting in concert with other cytokines, oncM may induce neuronal demise in both the developing and the mature brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HIV-1-infected individuals.
UR - http://www.scopus.com/inward/record.url?scp=0033563085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033563085&partnerID=8YFLogxK
M3 - Article
C2 - 10229874
AN - SCOPUS:0033563085
VL - 162
SP - 6268
EP - 6277
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -