caa a22 4500 475773217 CHVBK 20180406123623.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s001250051544 doi (NATIONALLICENCE)springer-10.1007/s001250051544 TNFα and IFNγ potentiate IL-1β induced mitogen activated protein kinase activity in rat pancreatic islets of Langerhans [Elektronische Daten] [N. Aa. Andersen, C. M. Larsen, T. Mandrup-Poulsen] Aims/hypothesis. Interleukin-1 beta (IL-1β) in synergy with tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) is cytotoxic to pancreatic beta cells. Mitogen-activated protein kinase (MAPK) activity that is induced by interleukin-1 beta has been suggested to signal nitric oxide-dependent as well as nitric oxide-independent beta-cell destructive pathways. The aim of this study was to investigate if TNFα and IFNγ signal through mitogen-activated protein kinases in isolated rat islets of Langerhans and if they potentiate mitogen-activated protein kinase activity induced by IL-1β.¶Methods. Islets of Langerhans were isolated from 5- to 7-day-old Wistar rats and precultured for 7 days before stimulation with IL-1β, TNFα and/or IFNγ for 20 min followed by lysis. Kinase activity was measured with a whole cell lysate kinase assay and after immunoprecipitation of the kinase using immunocomplex kinase assay.¶Results. Exposure to IL-1β or TNFα significantly increased mitogen-activated protein kinase activity, whereas IFNγ tended to decrease extracellular-signal-regulated kinase activity. Further, TNFα and IFNγ were found to synergistically increase mitogen-activated protein kinase activity induced by IL-1β.¶Conclusion/interpretation. We hypothesise that the synergistic effect of IL-1β, TNFα and IFNγ in the functional inhibition and induction of cell death in pancreatic beta cells is signalled through a synergistic activation of mitogen-activated protein kinase activity [Diabetologia (2000) 43: 1389-1396]. Springer-Verlag Berlin Heidelberg, 2000 Keywords c-jun N-terminal kinase, cytokines, ERK, extracellular-signal-regulated kinase, insulin-dependent diabetes mellitus, JNK, MAPK, p38, SAPK, signalling nationallicence Andersen N. Aa Steno Diabetes Center, Gentofte, Denmark, DK aut Larsen C. M. Steno Diabetes Center, Gentofte, Denmark, DK aut Mandrup-Poulsen T. Steno Diabetes Center, Gentofte, Denmark, DK aut https://doi.org/10.1007/s001250051544 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051544 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Andersen N. Aa Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Larsen C. M. Steno Diabetes Center, Gentofte, Denmark, DK aut NATIONALLICENCE 700 1- Mandrup-Poulsen T. Steno Diabetes Center, Gentofte, Denmark, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer