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.