Massive parallel gene expression profiling of RINm5F pancreatic islet beta-cells stimulated with interleukin-1beta.
Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to kill pancreatic beta-cells, and this unique property is thought to be involved in the pathogenesis of type I diabetes mellitus. We therefore determined the quantitative expression of 24,000 mRNAs of RINm5F, an insulinoma cell line derived from rat pancreatic beta-cells, before and after challenge with 30 and 1,000 pg/ml of recombinant human IL-1beta. The highest concentration resulted in decreased insulin production and cell death over a period of 4 days. Using three different time points, 2, 4 and 24 hours after challenge, we found that 146 full-length genes and a large number of expressed sequence tags were differentially regulated 3-fold or more. Most of the differentially regulated transcripts have not previously been described to be regulated by IL-1beta in beta-cells. We have analysed the expression data and sorted the genes into groups according to functional relations on the basis of knowledge of the structure or function ascribed to the individual genes. Many of the differentially regulated genes are known to play a role in immune- and stress-related pathways as well as in insulin secretion and vesicle trafficking, e.g. alpha-endosulfine and K+ channel Kir6.2 are differentially regulated. A number of transcripts in the biosynthesis pathway for cholesterol are also differentially regulated.
Rieneck
K
K
Institute for Inflammation Research, Dept. 7541, Rigshospitalet, National University Hospital, Copenhagen, Denmark. klausb@inet.uni2.dk
Bovin
L F
LF
Josefsen
K
K
Buschard
K
K
Svenson
M
M
Bendtzen
K
K
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D020869:Gene Expression Profiling; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D022161:Transport Vesicles
D016207:Cytokines; D029721:Drosophila Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D010455:Peptides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011994:Recombinant Proteins; C483180:endos protein, Drosophila; C075663:endosulfine