Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells
2000 (English)In: Blood, ISSN 0006-4971, Vol. 95, no 4, 1420-1426 p.Article in journal (Refereed) Published
Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor a (TNF-a), and CD40-ligation induced S-phase entry and mitosis in normal B cells and B-type chronic lymphocytic leukemia (B-CLL) cells. The viability of B-CLL cells stimulated by these protocols is high, and it has been hypothesized that the overexpression of Bcl-2 found in B-CLL protects the cells from apoptosis in vitro and in vivo. In this study, we have analyzed the response of cells derived from 12 samples of patients with B-CLL to recombinant human Trx in spontaneous apoptosis, with special reference to the Bcl-2 expression. Long-term cultures of B-CLL clones showed significantly higher viability when supplemented with human Trx (P = .031), also exemplified with clones surviving more than 2 months. Short-term cultures of B-CLL cells exposed to 1 ╡g/mL of Trx for 1,5, or 12 days maintained expression or delayed down-regulation of Bcl-2 compared with control cultures containing RPMI 1640 medium and 10% fetal calf serum only (P = .032, .002, .026, respectively). All B-CLL cells expressed constitutive Trx at varying but low levels. In contrast to adult T-cell leukemias, which overexpress Trx, as previously reported. We found that Trx added to B-CLL cells increased in a dose-dependent fashion the release of TNF-a, which has been suggested to be an autocrine growth factor for these cells. In conclusion, we have found that human recombinant Trx induced TNF-a secretion, maintained Bcl-2, and reduced apoptosis in B-CLL cells.
Place, publisher, year, edition, pages
2000. Vol. 95, no 4, 1420-1426 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-25285Local ID: 9725OAI: oai:DiVA.org:liu-25285DiVA: diva2:245613