Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2

Iwahashi, H.; Hanafusa, Takaaki; Eguchi, Y.; Nakajima, H.; Miyagawa, Junichi; Itoh, Noriyuki; Tomita, Kazuyoshi; Namba, Mitsuyoshi; Kuwajima, Masamichi; Noguchi, Takaaki; Tsujimoto, Yoshiaki; Matsuzawa, Y

doi:10.1007/s001250050475

Cited by 31 publications

(40 citation statements)

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“…The up-regulation by biliverdin/bilirubin of HO-1 would lead to an amplification cycle because more biliverdin is produced by the induced HO-1. In addition to the protective effect of HO-1, up-regulation of bcl-2 in ␤-cells can protect the cells from caspase-mediated cell death, thus contributing to the survival of transplanted islets (32)(33)(34). This is consistent with the suppressed level of caspases in freshly isolated islets and islet grafts at various days after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Bilirubin Can Induce Tolerance to Islet Allografts

et al. 2006

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Induction of heme oxygenase-1 (HO-1) expression in recipients of allogeneic islets can lead to long-term survival (>100 d) of those islets. We tested whether administration of bilirubin would substitute for the beneficial effects of HO-1 expression in islet transplantation. Administering bilirubin to the recipient (B6AF1) or incubating islets in a bilirubin-containing solution ex vivo led to long-term survival of allogeneic islets in a significant percentage of cases. In addition, administering bilirubin to only the donor frequently led to long-term survival of DBA/2 islets in B6AF1 recipients and significantly prolonged graft survival of BALB/c islets in C57BL/6 recipients. Donor treatment with bilirubin up-regulated mRNA expression of protective genes such as HO-1 and bcl-2 and suppressed proinflammatory and proapoptotic genes including monocyte chemoattractant protein-1 and caspase-3 and -8 in the islet grafts before transplantation. Furthermore, treatment of only the donor suppressed the expression of proinflammatory cytokines including TNF-alpha, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and other proapoptotic and proinflammatory genes normally seen in the islets after transplantation. Donor treatment also reduced the number of macrophages that infiltrated the islet grafts in the recipients. Preincubation of betaTC3 cells with bilirubin also protected the cells from lipid peroxidation. Our data suggests that the potent antioxidant and antiinflammatory actions of bilirubin may contribute to islet survival.

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Section: Discussionmentioning

confidence: 99%

Bilirubin Can Induce Tolerance to Islet Allografts

et al. 2006

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“…Addit i o n a l l y, the other transcriptional factors c-j u n and c-f o s, which are also implied in the signaling cascade leading to apoptosis, are induced by IL-1 in rat islets of Langerhans and RINm5F cells (49). In mouse pancreatic -cell lines ( TC1 and N I T-1), the combination of three cytokines (IL-1 , TNF-, and IFN-) was able to induce apoptotic cell death (50). Intere s t i n g l y, this study also showed that overexpression of b c l -2 in TC1 cells partially protected them from cytokine-induced death.…”

Section: A Role For Apoptosis In the Destruction Of -C E L L Smentioning

confidence: 98%

Apoptosis and the pathogenesis of IDDM: a question of life and death.

1998

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In type 1 diabetes, an immune-mediated process leads to the destruction of pancreatic beta-cells. In the last decade, considerable progress has been made in understanding the cellular and biochemical pathogenic processes of the disease. However, more needs to be learned about the immune mechanisms leading to the development of autoreactive immune cells and the molecular mechanisms of beta-cell death. The study of apoptosis of autoreactive lymphocytes as well as apoptosis of beta-cells may give answers to many still unsolved questions. This review focuses on the possible role of apoptosis both in the regulation of immune mechanisms involved in the pathogenesis of type 1 diabetes and as a way for beta-cells to die. The advancement in the knowledge of the possible role of apoptosis and its regulation in the pathogenesis of type 1 diabetes may provide new therapeutic tools for the prevention of the disease.

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“…When cells sense extracellular molecular cues, such as cytokines, growth factors or stress signals, they react in a wide variety of ways that may change their fate, leading to growth, death or differentiation [1][2][3][4]. Diverse post-translational modifications underlie these changes in cell state [5,6] and the ability to monitor such modifications is essential to make sense of cell physiology and to understand how its perturbation leads to pathological conditions.…”

Section: Introductionmentioning

confidence: 99%