Human T cell leukemia virus type-I Tax activates human macrophage inflammatory protein-3 alpha/CCL20 gene transcription via the NF-kappa B pathway

Int Immunol. 2002 Feb;14(2):147-55. doi: 10.1093/intimm/14.2.147.

Abstract

Infection by human T cell leukemia virus type (HTLV)-I is associated with several diseases, including adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Leukocytes are attracted to the sites of inflammation by chemotactic factors. Macrophage inflammatory protein (MIP)-3 alpha/CCL20 is a recently isolated member of the CC subfamily of chemokines and has been proposed as a crucial factor to elicit inflammatory reactions. We now report that endogenous MIP-3 alpha mRNA levels are elevated in HTLV-I-infected T cell lines and in a human T cell line following the induced expression of the HTLV-I-encoded transactivator, Tax. Analysis of the human MIP-3 alpha promoter revealed that this gene is activated by Tax, via the activation of nuclear factor (NF)-kappa B, whose responsive element, -82-kappa B, is located at a position between -82 and -91 relative to the putative transcription start site. With an electromobility shift assay we further demonstrated that the -82-kappa B element was bound by the Tax-activated p50/p65 heterodimers of NF-kappa B. Expression of the specific receptor of MIP-3 alpha, CCR6, was also increased in HTLV-I-infected T cell lines, suggesting an autocrine and/or paracrine mechanism to establish the pathogenesis of HTLV-I-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL20
  • Chemokines, CC / genetics*
  • Gene Products, tat / physiology*
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Jurkat Cells
  • Macrophage Inflammatory Proteins / genetics*
  • NF-kappa B / physiology*
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Receptors, CCR6
  • Receptors, Chemokine / analysis
  • Transcription, Genetic*

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • Chemokine CCL20
  • Chemokines, CC
  • Gene Products, tat
  • Macrophage Inflammatory Proteins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, CCR6
  • Receptors, Chemokine