Lack of expression of Gp-130 makes pancreatic beta cell lines unresponsive to the IL-6 family of cytokines.
Cytokine receptors from the IL-6 receptor family are comprised of ligand specific alpha chains and a common signalling chain, gp-130, which is also required for high affinity binding. A cDNA library generated from the beta-TC3 SV40 T-antigen transformed insulinoma cell line was screened for members of this receptor family potentially relevant to both beta cell development and autoimmunity. Degenerate oligonucleotide primers to a consensus region of these receptors were used and the IL-11 receptor alpha chain was identified. Despite confirmation of IL-11 receptor mRNA expression, iodinated bioactive IL-11 did not bind specifically to beta-TC3 cells and gp-130-dependent cytokines did not elicit signalling events in beta cell lines. This was explained by absence of gp-130 protein or mRNA in the beta cell lines tested and in primary islets. We conclude from these results that the previously recognised effects of IL-6 family member cytokines on pancreatic islets must be indirect via other non-beta cells within the islet, rather than due to direct effects on beta cells themselves.
Naselli
G
G
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.
Deaizpurua
H J
HJ
Thomas
H E
HE
Johnston
A M
AM
Kay
T W
TW
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis; D019281:Dimerization; D015870:Gene Expression; D007340:Insulinoma / Q000378:metabolism; D017370:Interleukin-11 / Q000378:metabolism / Q000494:pharmacology; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009025:Morpholines / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D018121:Receptors, Cytokine / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053702:Receptors, Interleukin-11; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C508429:Il11ra1 protein, mouse; C508431:Il11ra2 protein, mouse; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; D009025:Morpholines; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C005759:2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine