Key result
Oncostatin M cuts HIV-1 Tat-mediated trans-activation ~50% in HLtat cells but lacks broader anti-HIV activity.
Oncostatin M inhibits HIV-1 Tat-mediated trans-activation specifically in HLtat cells but not in other cell lines, highlighting the importance of selecting appropriate in vitro models for screening HIV inhibitors.
Cell-line specificity cautions against clinical translation; leaves open Oncostatin M antiviral utility and underscores model validation in HIV screening.
We have tested the effect of oncostatin M (OSM) on the Tat-mediated trans-activation in a HeLa cell line (HLtat) expressing Tat, using a transfection assay with the LacZ gene under the control of the HIV-1 LTR. Oncostatin M reduced the LacZ expression by 50% at a concentration of 9.5 ng/ml (IC50), which was far below the 50% cytotoxic concentration (CC50 > 400 ng/ml). Although HLtat cells may represent an interesting model for the study of the signal transduction pathway of OSM, this cytokine did not inhibit the tumor necrosis factor (TNF)-dependent activation of the HIV LTR in Molt pNAZ cells or the Tat-mediated trans-activation in HeLa, HeLa-CD4, Hep-II, COS-7, or Jurkat-tat cells. Likewise, OSM did not show any anti-HIV-1 activity in the MT4 cell/MTT assay. Our findings with OSM indicate that, for the screening of HIV Tat inhibitors, care must be taken in selecting a system that not only emulates HIV Tat trans-activation, but is also representative for in vivo-infected cells.
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Esté et al. (1995) studied HIV-1 Tat-mediated trans-activation. Oncostatin M (OSM) was evaluated on LacZ expression (Tat-mediated trans-activation). Oncostatin M reduced HIV-1 Tat-mediated trans-activation by 50% at 9.5 ng/ml in HLtat cells, but failed to inhibit trans-activation in other cell lines or show anti-HIV-1 activity in MT4 cells.
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