HTLV-I Tax protein inhibits apoptosis induction but not G1 arrest by pyrrolidinedithiocarbamate, an anti-oxidant, in adult T cell leukemia cells

Arima, Naomichi; Arimura, Kosei; Tokito, Yuichi; Sakaki, Yoshimune; Matsushita, Kakushi; Orihara, Koji; Akimoto, Masaki; Ozaki, Atsuo; Kukita, Toshimasa; Hagiwara, Takafumi; Hamada, Hciichiro

doi:10.1016/j.exphem.2003.11.008

Cited by 31 publications

(22 citation statements)

References 56 publications

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“…PD-L1 expression on the CD4 þ CD25 lymphocytes appeared to vary among individuals. Such variation is also seen in vitro; the cloned HTLV-1-infected Oh13T cell line and HTLV-1-negative Jurkat cell line expressed PD-L1, whereas HTLV-1-infected Su9TO1, K3T, F6T, SlT 38 and HTLV-1-negative MOLT-4 and KG-1 had no measurable PD-L1 expression (data not shown). The percentage of PD-L1 expression on CD4 þ CD25 þ cells was summarized in Figure 2c along with the percentage of PD-1 expression in CD8 þ lymphocytes.…”

Section: Pd-l1 Expression In Acs and Atll Patientsmentioning

confidence: 83%

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

et al. 2008

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Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1/ programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1/ PD-L1 pathway could be involved in the establishment of persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1 expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically elevated. In addition, PD-1 expression was significantly higher on CD8 þ T cells along with cytomegalovirus (CMV)-and Epstein-Barr virus (EBV)-specific CTLs in ATLL patients compared with ACs and control individuals. Primary ATLL cells in 21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not observed in cells from ACs. Finally, in functional studies, we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8 þ T-cell response. These observations suggest that the PD-1/ PD-L1 pathway plays a role in fostering persistent HTLV-1 infections, which may further ATLL development and facilitate immune evasion by ATLL cells.

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Section: Pd-l1 Expression In Acs and Atll Patientsmentioning

confidence: 83%

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

et al. 2008

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“…[14][15][16][17] Controversial reports exist on effects of PDTC on apoptosis. 18 Significant contribution may be obtained from the effects of PDTC for alleviation and restoration of I/R injury in testis. Hopefully, our results may inspire further trials investigating the applications of PDTC in other diseases associated with I/R injury.…”

Section: Discussionmentioning

confidence: 99%

An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis

Kemahlı

Yildiz

Fırat

et al. 2016

CUAJ

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Introduction: The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-kβ, on ischemiareperfusion injury in rats. Methods: A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and 3 underwent testicular torsion of 720° for four hours and 100 mg/ kg of PDTC was administered intraperitoneally prior to detorsion in Group 3. An hour after detorsion process, left orchiectomies were performed and 5 ml of intracardiac blood samples were drawn from rats in all three groups. Histopathological examination of testis tissues performed and measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in blood samples were taken. Results: Elevated levels of MDA and decreased SOD activity, together with decreased Johnson tubular biopsy scores consistent with I/R injury were observed in Group 2 (p<0.05). Group 1 and Group 3 were similar in terms of MDA levels, SOD activity, and Johnson scores (p>0.05). Conclusions: Our results indicated that PDTC may have beneficial effects for alleviation of I/R injury in testicular tissue in rats. Understanding the underlying mechanisms and exploration of its diagnostic and therapeutic potential requires further randomized, controlled trials on a larger scale.

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“…Whole cell lysates were prepared as described previously [Arima et al, 2004]. The collected cells cultured with or without various concentrations of cyclosporin A were lysed in lysis solution [20 mM Tris pH 8.0, 150 mM NaCl, 1 mM EDTA, 1% Triton X-100, 1 mM phenylmethylsulfonyl fluoride (PMSF)].…”

Section: Western Blot For Tax and Atf Proteinsmentioning

confidence: 99%

Cyclosporin a inhibits HTLV‐I tax expression and shows anti‐tumor effects in combination with VP‐16

Ozaki¹,

Arima²,

Matsushita³

et al. 2007

Journal of Medical Virology

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Adult T cell leukemia (ATL) is one of the most refractory malignant hematological diseases. Our previous studies demonstrated HTLV-1Tax protein involvement in clinical manifestation of the aggressive type of ATL and suggested the potential application of agents to inhibit Tax expression for ATL treatment. In the present study, we first examined Tax involvement in the resistance to VP-16-induced apoptosis using four HTLV-1 infected T cell clones and cTax DNA-transfected cells. Next, we examined whether cyclosporin A reduced expression of Tax and its related transfer factors on Western blot and CAT assay. We further investigated whether cyclosporin A in combination with VP-16 can induce apoptosis in HTLV-1 infected T cells. Tax-producing T cells, K3T and F6T, were resistant to VP-16 induced growth inhibition compared with that of the nonproducing cells, S1T and Su9T01. Experiments using S1T and Tax-expressing cDNA-transfected S1T demonstrated Tax-induced resistance to VP-16 induction of apoptosis by DNA ladder formation. Cyclosporin A reduced Tax expression in K3T by Western blot analysis and on CAT assay, showing maximal reduction of 61% and 60% compared to control culture using LTR CAT transfected Jurkat cells and K3T cells, respectively. Cyclosporin A also reduced the nuclear expression of two Tax-related transfer factors, ATF-1 and ATF-2 on Western blot. Cyclosporin A alone did not show any cytotoxicity by itself, but sensitized cells to VP-16 when combined with VP-16. Cyclosporin A may be a useful anti-ATL agent when combined with other anti-cancer agents possibly related to Tax inhibition.

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HTLV-I Tax protein inhibits apoptosis induction but not G1 arrest by pyrrolidinedithiocarbamate, an anti-oxidant, in adult T cell leukemia cells

Cited by 31 publications

References 56 publications

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis

Cyclosporin a inhibits HTLV‐I tax expression and shows anti‐tumor effects in combination with VP‐16

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