Involvement of p38 MAPK signaling pathway in IFN-gamma and HTLV-I expression in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.

Abstract

We analyzed the relationship between the expression of interferon (IFN)-gamma and HTLV-I p19 antigen and activation of p38 mitogen-activated protein kinase (p38 MAPK) in two HTLV-I-infected T cell lines derived from two patients (HCT-1 and HCT-4) with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and three HTLV-I-infected T cell lines derived from three patients with adult T cell leukemia (ATL). Expression of phosphorylated (activated)-p38 MAPK was markedly increased concomitant with high levels of both IFN-gamma and HTLV-I p19 antigen expression in both HCT-1 and HCT-4 compared with cell lines derived from ATL patients. Treatment with SB203580, a specific inhibitor of p38 MAPK, suppressed IFN-gamma and HTLV-I p19 antigen expression levels in HCT-1, HCT-4 and peripheral blood CD4(+) T cells of HAM/TSP patients. These findings strongly suggest that activation of p38 MAPK signaling pathway is involved in the up-regulation of IFN-gamma expression with high HTLV-I proviral load in HAM/TSP patients.

• Authors: Naomi Fukushima, Yoshihiro Nishiura, Tatsufumi Nakamura, Yasuaki Yamada, Shigeru Kohno, Katsumi Eguchi
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 159 Issue 1-2 Pg. 196-202 (Feb 2005) ISSN: 0165-5728 [Print] Netherlands
• PMID: 15652420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Gene Products, gag
• HTLV-I Antigens
• Imidazoles
• Protein Kinase Inhibitors
• Pyridines
• Retroviridae Proteins, Oncogenic
• gag Gene Products, Human Immunodeficiency Virus
• p19 protein, Human T-lymphotropic virus 1
• Interferon-gamma
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Adult
• Aged
• Antiviral Agents (pharmacology)
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism, virology)
• Cell Line
• Female
• Gene Products, gag (antagonists & inhibitors, biosynthesis)
• HTLV-I Antigens (biosynthesis)
• Human T-lymphotropic virus 1 (immunology)
• Humans
• Imidazoles (pharmacology)
• Interferon-gamma (antagonists & inhibitors, biosynthesis)
• MAP Kinase Signaling System (immunology)
• Male
• Middle Aged
• Paraparesis, Tropical Spastic (enzymology, immunology, virology)
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Proviruses (immunology)
• Pyridines (pharmacology)
• Retroviridae Proteins, Oncogenic (antagonists & inhibitors, biosynthesis)
• T-Lymphocytes (drug effects, enzymology, immunology, virology)
• gag Gene Products, Human Immunodeficiency Virus
• p38 Mitogen-Activated Protein Kinases (biosynthesis, metabolism, physiology)