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.

Abstract

BACKGROUND:

Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, 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.

• Authors: Mineki Saito, Hiroe Sejima, Tadasuke Naito, Hiroshi Ushirogawa, Toshio Matsuzaki, Eiji Matsuura, Yuetsu Tanaka, Tatsufumi Nakamura, Hiroshi Takashima
• Journal: Virology journal (Virol J) Vol. 14 Issue 1 Pg. 234 (12 04 2017) ISSN: 1743-422X [Electronic] England
• PMID: 29202792 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Chemokine CCL1
• Gene Products, tax
• Receptors, CCR8
• Minocycline

Topics

• Adult
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Cell Line
• Chemokine CCL1 (genetics, metabolism)
• Down-Regulation (drug effects)
• Flow Cytometry
• Gene Products, tax (metabolism)
• Humans
• Minocycline (pharmacology, therapeutic use)
• Paraparesis, Tropical Spastic (drug therapy, physiopathology)
• Promoter Regions, Genetic
• Real-Time Polymerase Chain Reaction
• Receptors, CCR8 (metabolism)
• Transcriptional Activation (drug effects)
• Up-Regulation (genetics)