| First Author | Waelput W | Year | 2001 |
| Journal | J Exp Med | Volume | 194 |
| Issue | 11 | Pages | 1617-24 |
| PubMed ID | 11733576 | Mgi Jnum | J:73099 |
| Mgi Id | MGI:2154571 | Doi | 10.1084/jem.194.11.1617 |
| Citation | Waelput W, et al. (2001) A mediator role for metallothionein in tumor necrosis factor-induced lethal shock. J Exp Med 194(11):1617-24 |
| abstractText | Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is centrally involved in several inflammatory disorders. Administration of TNF leads to a potentially lethal systemic inflammatory response syndrome (SIRS). We observed that (a) mice lacking functional genes for metallothionein 1 and 2 (MT-null) were protected compared with wild-type controls (P = 0.0078), and (b) mice overexpressing MT-1 (MT-TG) were more sensitized for the lethal effect of TNF than control mice (P = 0.0003), indicating a mediating role for MT in TNF induced SIRS. As MT is involved in the body zinc homeostasis, we tested whether zinc-deprivation or -supplementation alters the response to TNF. Although zinc-depletion strongly sensitized (P = 0.036), and pretreatment with zinc sulfate (ZnSO4) conferred protection against the deleterious effects of TNF (P < 0.0002), it was also found that the protection provided by zinc is independent of MT. Our observation that hsp70 is strongly induced in jejunum after ZnSO4 treatment, suggests a contribution of hsp70 in the protection against TNF. In addition, ZnSO4 cotreatment allowed complete regression of inoculated tumors with TNF and interferon gamma, leading to a significantly better survival (P = 0.0045). |
