Involvement of p38 MAPK signaling pathway in IFN-gamma and HTLV-I expression in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
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.
Fukushima
Naomi
N
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Nishiura
Yoshihiro
Y
Nakamura
Tatsufumi
T
Yamada
Yasuaki
Y
Kohno
Shigeru
S
Eguchi
Katsumi
K
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D005260:Female; D015683:Gene Products, gag / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015486:HTLV-I Antigens / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011533:Proviruses / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000821:virology; D054301:gag Gene Products, Human Immunodeficiency Virus; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
D000998:Antiviral Agents; D015683:Gene Products, gag; D015486:HTLV-I Antigens; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C060955:p19 protein, Human T-lymphotropic virus 1; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580