Interleukin-10 gene expression in adult T-cell leukemia

Blood. 1996 Aug 1;88(3):1035-45.

Abstract

We studied the serum levels of interleukin-10 (IL-10), in patients with adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) infection. Elevated IL-10 levels were observed in 33 of 45 patients with ATL. Fresh leukemic cells from ATL patients as well as HTLV-I-infected T-cell lines MT-2, SLB-1, and C10/MJ expressed IL-10 mRNA by reverse transcription-polymerase chain reaction analysis, whereas IL-10 mRNA was not detected in normal peripheral mononuclear cells and an uninfected T-cell line Jurkat. IL-10 protein was also detected in the culture medium of leukemic cells from ATL patients as well as these HTLV-I-infected cell lines, and in the extracellular fluids of ATL patients. Interestingly, MT-4 cells, which did not express Tax although transformed by HTLV-I, did not express IL-10 at either the mRNA or protein level. To elucidate the role of the HTLV-I encoded transactivator Tax in IL-10 gene expression, Jurkat cells were transfected with a Tax expression plasmid. In transiently transfected Jurkat cells, endogenous IL-10 mRNA expression was induced by Tax. Stably transfected Jurkat cell lines expressed IL-10 mRNA and secreted IL-10 protein into the culture medium. The nuclear factor (NF)-kappa B pathway is a target for Tax transactivation. We treated MT-2 cells with phosphorothioate antisense oligonucleotides to the p65 subunit of NF-kappa B. A reduction in the expression of p65 was accompanied by a reduction in IL-10 gene expression and IL-10 production. We showed that the IL-10 kappa B-like sites ( kappa B1,-2,034 to -2,025; kappa B2, -1,961 to -1,952; kappa B3, -452 to -443) specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2 cells and that NF-kappa B bound with the highest affinity to the kappa B2 element (kappa B2 > kappa B3 > kappa B1). These data suggest a general role for NF-kappa B activation in the induction of IL-10 gene transcription. Activation of IL-10 in HTLV-I-infected cells may contribute to the pathology associated with HTLV-I infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Body Fluids / chemistry
  • Gene Expression Regulation, Leukemic*
  • Gene Products, tax / metabolism
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / blood
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Macromolecular Substances
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Regulatory Sequences, Nucleic Acid
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Gene Products, tax
  • Macromolecular Substances
  • NF-kappa B
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Interleukin-10