Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells

Suhayl Dhib-Jalbut, Paul M. Hoffman, Toshio Yamabe, Di Sun, Jane Xia, Howard Eisenberg, Gregory K Bergey, Francis W. Ruscetti

Research output: Contribution to journalArticle

Abstract

Tropical spastic paraparesis (HAM/TSP) is caused by human T-cell lymphotropic virus type I (HTLV-1) 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-1β (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.

Original languageEnglish (US)
Pages (from-to)787-790
Number of pages4
JournalAnnals of Neurology
Volume36
Issue number5
DOIs
StatePublished - Nov 1994
Externally publishedYes

Fingerprint

tax Gene Products
Microglia
Cytokines
Viruses
T-Lymphocytes
Demyelinating Diseases
Interleukin-1
Interleukin-6
Tumor Necrosis Factor-alpha
Reverse Transcription
Deltaretrovirus Infections
Macrophages
Tropical Spastic Paraparesis
Inflammation
Nerve Tissue
Polymerase Chain Reaction
Human T-lymphotropic virus 1
Central Nervous System
Enzyme-Linked Immunosorbent Assay
Messenger RNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dhib-Jalbut, S., Hoffman, P. M., Yamabe, T., Sun, D., Xia, J., Eisenberg, H., ... Ruscetti, F. W. (1994). Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells. Annals of Neurology, 36(5), 787-790. https://doi.org/10.1002/ana.410360516

Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells. / Dhib-Jalbut, Suhayl; Hoffman, Paul M.; Yamabe, Toshio; Sun, Di; Xia, Jane; Eisenberg, Howard; Bergey, Gregory K; Ruscetti, Francis W.

In: Annals of Neurology, Vol. 36, No. 5, 11.1994, p. 787-790.

Research output: Contribution to journalArticle

Dhib-Jalbut, Suhayl ; Hoffman, Paul M. ; Yamabe, Toshio ; Sun, Di ; Xia, Jane ; Eisenberg, Howard ; Bergey, Gregory K ; Ruscetti, Francis W. / Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells. In: Annals of Neurology. 1994 ; Vol. 36, No. 5. pp. 787-790.
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