We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis.
- Authors
Mineki Saito; Hiroe Sejima; Tadasuke Naito; Hiroshi Ushirogawa; Toshio Matsuzaki; Eiji Matsuura; Yuetsu Tanaka; Tatsufumi Nakamura; Hiroshi Takashima
- Abstract
Background: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/macrophages and Tlymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Results: The results showed that: (1) CCL1 was preferentially expressed in HAM/TSP-derived HTLV-1-infected T-cell lines, (2) CCL1 expression was induced along with Tax expression in the Tax-inducible T-cell line JPX9, (3) transient Tax expression in an HTLV-1-negative T-cell line activated the CCL1 gene promoter, (4) plasma levels of CCL1 were significantly higher in patients with HAM/TSP than in HTLV-1-seronegative patients with multiple sclerosis and HTLV-1-infected asymptomatic healthy carriers, and (5) minocycline inhibited the production of CCL1 in HTLV-1- infected T-cell lines. Conclusions: The present results suggest that elevated CCL1 levels may be associated with the pathogenesis of HAM/TSP. Although further studies are required to determine the in vivo significance, minocycline may be considered as a potential candidate for the long-term treatment of HAM/TSP via its anti-inflammatory effects, which includes the inhibition of CCL1 expression.
- Subjects
HTLV-I infections; CHEMOKINES; MINOCYCLINE; SPINAL cord diseases; PARAPARESIS; T cells; THERAPEUTICS
- Publication
Virology Journal, 2017, Vol 14, p1
- ISSN
1743-422X
- Publication type
Article
- DOI
10.1186/s12985-017-0902-6