Details

Autor(en) / Beteiligte

• Paul, Nina L.
• Millet, Isabelle
• Ruddle, Nancy H.

Titel

The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-κB in human T-cell lines

Ist Teil von

• Cytokine (Philadelphia, Pa.), 1993-07, Vol.5 (4), p.372-378

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

1993

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-β) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-κB site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-κB construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-κB in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-κB that directly bound to the LT-κB site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and κB-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of MI-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-κB.