This laboratory has reported that multiple low doses of streptozotocin (MLD-STZ) similarly upregulate the T helper (Th)1-type proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in islets of both the diabetes-susceptible male and the diabetes-resistant female C57BL/6 mice and that MLD-STZ downregulates the anti-inflammatory Th2-type cytokines interleukin (IL)-4 and IL-10, as well as the anti-inflammatory Th3-type cytokine-transforming growth factor (TGF)-ss1 in islets of male, but not female, mice. Thus, diabetes is associated with a relative preponderance of local proinflammatory cytokines. Here, we investigated the effects of MLD-STZ on the anti-inflammatory cytokine IL-11 and the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, which are involved in gene activation of proinflammatory cytokines, and on the cytosolic kinase (IKK-alpha) of NF-kappaB inhibitor (IkappaB). Furthermore, the effect of recombinant human (rh)IL-11 on MLD-STZ diabetes, insulitis, cytokines, IKK-alpha, NF-kappaB, and AP-1 was analyzed in islets. Interleukin-11 prevented diabetes without affecting insulitis; attenuated TNF-alpha and IFN-gamma response; and stimulated IL-4 production and inhibited activation of IKK-alpha, NF-kappaB, and AP-1. The results demonstrated the potential of rhIL-11 in preventing MLD-STZ diabetes through enhancement of anti-inflammatory responses in islets. In this process, the transcription factors NF-kappaB and AP-1 might play a key role.
|Titolo:||Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice|
|Data di pubblicazione:||2004|
|Citazione:||Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice / LGSSIAR A; HASSAN M; SCHOTT-OHLY P; FRIESEN N; NICOLETTI F; TREPICCHIO WL; GLEICHMANN H. - In: EXPERIMENTAL BIOLOGY AND MEDICINE. - ISSN 1535-3702. - 229(5)(2004), pp. 425-436.|
|Appare nelle tipologie:||1.1 Articolo in rivista|