Cytokine-induced human islet cell death in vitro correlates with a persistently high phosphorylation of STAT-1, but not with NF-κB activation

Henrietta Hindlycke, Tao Lu, Nils Welsh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Studies of insulin producing β-cells have reported conflicting responses to NF-κB activation, encompassing both pro- and anti-apoptotic effects, possibly reflecting the use of β-cells from different species. Therefore, the aim of this study was to compare the temporal activation of NF-κB in rat and human insulin producing cells and relate this to the dynamics of cell death, STAT-1 activation and the production of nitric oxide (NO). Rat RIN5AH and human islet cells were exposed to the cytokines IL-1β and IFN-γ and the NOS inhibitor aminoguanidine. Cell death, NO production, IκBα phosphorylation, p65 methylation, STAT-1 phosphorylation and cIAP-2 levels were analyzed at different time-points. Cytokine-induced RIN5AH cell death occurred on day 1, and this was paralleled by NF-κB activation, STAT-1 phosphorylation and production of NO. On the other hand, the human islet cells instead died by an NO-independent mechanism on day 3 and 5. This later occurring cell death was associated with a gradual decrease in IκBα phosphorylation and p65 methylation, and a lowered expression of the NF-κB target genes IκBα and cIAP-2. STAT-1 phosphorylation was persistently high during the entire cytokine exposure period in human islet cells. The results favor a pro-survival role of NF-κB and a pro-apoptotic role of STAT-1 in human islet cells. Thus, rodent insulin producing cells may not be suitable as models for human β-cells in the context of cytokine-induced damage.

Original languageEnglish (US)
Pages (from-to)845-850
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume418
Issue number4
DOIs
StatePublished - Feb 24 2012

Fingerprint

Phosphorylation
Cell death
Islets of Langerhans
Cell Death
Chemical activation
Cytokines
Nitric Oxide
Methylation
Insulin
Rats
Interleukin-1
Genes
In Vitro Techniques
Rodentia

Keywords

  • Apoptosis
  • Cytokines
  • Human islets
  • NF-κB
  • Nitric oxide
  • STAT-1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Cytokine-induced human islet cell death in vitro correlates with a persistently high phosphorylation of STAT-1, but not with NF-κB activation. / Hindlycke, Henrietta; Lu, Tao; Welsh, Nils.

In: Biochemical and Biophysical Research Communications, Vol. 418, No. 4, 24.02.2012, p. 845-850.

Research output: Contribution to journalArticle

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