TY - JOUR
T1 - Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis
AU - Zhao, Meng Liang
AU - Kim, Mee Ohk
AU - Morgello, Susan
AU - Lee, Sunhee C.
N1 - Funding Information:
This study was supported by MH55477. We are grateful to the staff and participants in the Manhattan HIV Brain Bank (R24MH59724), to Dr. Sue Griffin for providing the detailed protocol for IL-1 immunostain, Dr. David Goldman for critical reading of the manuscript and contributing Fig. 2 , and Dr. Marty Sliwinski for the statistical analysis. We also thank Drs. Dennis Dickson, Celia Brosnan, Moon Shin, and Martha Downen for their support throughout the study.
PY - 2001/4/2
Y1 - 2001/4/2
N2 - Inflammatory cytokines and enzymes such as IL-1 and inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of AIDS dementia, a condition associated with infection of the CNS cells by the HIV-1. In this report, we investigated the expression of iNOS, IL-1, and caspase-1 (interleukin-1 converting enzyme) in HIV-1 encephalitis (HIVE) by immunocytochemistry and analyzed their expression with respect to HIV-1 infection and glial activation. In HIVE, all three molecules were expressed at high levels in areas of HIV-1 infection (microglial nodules with HIV-1 p24 immunoreactivity) and in areas of diffuse white matter gliosis. Expression was cell-type specific, with IL-1 and caspase-1 being expressed in macrophages and microglia, and iNOS in activated astrocytes. Multinucleated giant cells, a hallmark of virally infected cells, showed intense staining for both IL-1 and caspase-1, suggesting induction of these molecules by HIV-1. Double immunocytochemistry demonstrated a regional co-localization of astrocyte iNOS and microglial IL-1 and caspase-1. These results support the notion that autocrine and paracrine interactions between HIV-1 infected macrophages and microglia, activated microglia, and astrocytes lead to expression of proinflammatory and neurotoxic molecules. iNOS and caspase-1 may provide additional therapeutic targets for HIVE.
AB - Inflammatory cytokines and enzymes such as IL-1 and inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of AIDS dementia, a condition associated with infection of the CNS cells by the HIV-1. In this report, we investigated the expression of iNOS, IL-1, and caspase-1 (interleukin-1 converting enzyme) in HIV-1 encephalitis (HIVE) by immunocytochemistry and analyzed their expression with respect to HIV-1 infection and glial activation. In HIVE, all three molecules were expressed at high levels in areas of HIV-1 infection (microglial nodules with HIV-1 p24 immunoreactivity) and in areas of diffuse white matter gliosis. Expression was cell-type specific, with IL-1 and caspase-1 being expressed in macrophages and microglia, and iNOS in activated astrocytes. Multinucleated giant cells, a hallmark of virally infected cells, showed intense staining for both IL-1 and caspase-1, suggesting induction of these molecules by HIV-1. Double immunocytochemistry demonstrated a regional co-localization of astrocyte iNOS and microglial IL-1 and caspase-1. These results support the notion that autocrine and paracrine interactions between HIV-1 infected macrophages and microglia, activated microglia, and astrocytes lead to expression of proinflammatory and neurotoxic molecules. iNOS and caspase-1 may provide additional therapeutic targets for HIVE.
KW - AIDS
KW - Astrocyte
KW - Cytokine
KW - Dementia
KW - Microglia
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U2 - 10.1016/S0165-5728(00)00463-X
DO - 10.1016/S0165-5728(00)00463-X
M3 - Article
C2 - 11282169
AN - SCOPUS:0035795058
SN - 0165-5728
VL - 115
SP - 182
EP - 191
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
IS - 1-2
ER -
