TY - JOUR
T1 - Extracellular human T‐cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells
AU - Dhib‐Jalbut, Suhayl
AU - Hoffman, Paul M.
AU - Yamabe, Toshio
AU - Sun, Di
AU - Xia, Jane
AU - Eisenberg, Howard
AU - Bergey, Gregory
AU - Ruscetti, Francis W.
PY - 1994/11
Y1 - 1994/11
N2 - Tropical spastic paraparesis (HAM/TSP) is caused by human T‐cell lymphotropic virus type I (HTLV‐I) infection. Although the virus infects T cells in vivo and is capable of infecting microglia in vitro, the inflammatory demyelination has not been linked to virus in central nervous system tissue. Thus, indirect mechanisms (e.g., cytokines) could be involved in demyelination and inflammation. The ability of HTLV‐I Tax protein to induce tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), and IL‐6 in primary adult human microglia and peripheral blood macrophages (PBMs) was examined by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction (RT‐PCR). Tax (20 ng/ml) induced TNF‐α in microglia (from undetectable or low basal levels to 215–1,075 pg/ml, mean 576 ± 375 pg/ml, n = 4) and in PBMs (70‐1,900, mean 646 ± 844 pg/ml, n = 4). This induction was dose dependent, Tax specific, and maximal at 8 hours after stimulation. IL‐6 levels in microglia increased from a basal level of 368 ± 194 to 664 ± 270 pg/ml 24 hours after Tax stimulation. In contrast, IL‐1β levels were modestly induced (≤26 pg/ml). An increase in mRNA levels of the three cytokines was observed by semiquantitative RT‐PCR (TNF‐α = 28‐fold; IL‐6 = 5.6‐fold; IL‐1β = 3.6‐fold). Thus, in HAM/TSP, extracellular Tax released from infiltrating T cells could induce cytokine release by microglia and contribute to demyelination and inflammation in the absence of detectable virus.
AB - Tropical spastic paraparesis (HAM/TSP) is caused by human T‐cell lymphotropic virus type I (HTLV‐I) infection. Although the virus infects T cells in vivo and is capable of infecting microglia in vitro, the inflammatory demyelination has not been linked to virus in central nervous system tissue. Thus, indirect mechanisms (e.g., cytokines) could be involved in demyelination and inflammation. The ability of HTLV‐I Tax protein to induce tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), and IL‐6 in primary adult human microglia and peripheral blood macrophages (PBMs) was examined by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction (RT‐PCR). Tax (20 ng/ml) induced TNF‐α in microglia (from undetectable or low basal levels to 215–1,075 pg/ml, mean 576 ± 375 pg/ml, n = 4) and in PBMs (70‐1,900, mean 646 ± 844 pg/ml, n = 4). This induction was dose dependent, Tax specific, and maximal at 8 hours after stimulation. IL‐6 levels in microglia increased from a basal level of 368 ± 194 to 664 ± 270 pg/ml 24 hours after Tax stimulation. In contrast, IL‐1β levels were modestly induced (≤26 pg/ml). An increase in mRNA levels of the three cytokines was observed by semiquantitative RT‐PCR (TNF‐α = 28‐fold; IL‐6 = 5.6‐fold; IL‐1β = 3.6‐fold). Thus, in HAM/TSP, extracellular Tax released from infiltrating T cells could induce cytokine release by microglia and contribute to demyelination and inflammation in the absence of detectable virus.
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U2 - 10.1002/ana.410360516
DO - 10.1002/ana.410360516
M3 - Article
C2 - 7979225
AN - SCOPUS:0028006939
SN - 0364-5134
VL - 36
SP - 787
EP - 790
JO - Annals of neurology
JF - Annals of neurology
IS - 5
ER -