The precursor but not the mature form of IL1alpha blocks the release of FGF-1 in response to heat shock.

Interleukin (IL)1α mediates proinflammatory events through its extracellular interaction with the IL1 type I receptor. However, IL1α does not contain a conventional signal peptide sequence that provides access to the endoplasmic reticulum-Golgi apparatus for secretion. Thus, we have studied the release of the precursor (p) and mature (m) forms of IL1α from NIH 3T3 cells. We have demonstrated that mIL1α but not pIL1α was released in response to heat shock with biochemical and pharmacological properties similar to those reported for the stress-mediated release pathway utilized by fibroblast growth factor (FGF)1. However, unlike the FGF1 release pathway, the IL1α release pathway appears to function independently of synaptotagmin (Syt)1 because the expression of a dominant-negative form of Syt1, which represses the release of FGF1, did not inhibit the release of mIL1α in response to temperature stress. Interestingly, whereas the expression of both mIL1α and FGF1 in NIH 3T3 cells did not impair the stress-induced release of either polypeptide, the expression of both pIL1α and FGF1 repressed the release of FGF1 in response to temperature stress. These data suggest that the release of mIL1α requires proteolytic processing of its precursor form and that mIL1α and FGF1 may utilize similar but distinct mechanisms for export.