TNF-beta produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts.
Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT-2 supernatants were found to be dose dependent and were reduced by heat treatment at 100 degrees C for 5 min, but not at 56 degrees C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-alpha and rTNF-beta also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30-kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-beta mAb, although they were not blocked by anti-TNF-alpha mAb. In a Western blot assay, the 25- and 27-kDa bands of TNF-beta were shown clearly in the HUT102 supernatant, although no TNF-alpha bands appeared. These findings suggest that TNF-beta is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts.
Yu
F
F
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Itoyama
Y
Y
Kira
J
J
Fujihara
K
K
Kobayashi
T
T
Kitamoto
T
T
Suzumura
A
A
Yamamoto
N
N
Nakajima
Y
Y
Goto
I
I
D002455:Cell Division; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005910:Glioma / Q000473:pathology; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000473:pathology
D016207:Cytokines; D008233:Lymphotoxin-alpha