The precursor but not the mature form of IL1 alpha blocks the release of FGF1 in response to heat shock

Interleukin (IL)1 alpha mediates proinflammatory events through its extrace llular interaction with the IL1 type I receptor. However, IL1 alpha does no t contain a conventional signal peptide sequence that provides access to th e endoplasmic reticulum-Golgi apparatus for secretion. Thus, we have studie d the release of the precursor (p) and mature (m) forms of IL1 alpha from N IH 3T3 cells. We have demonstrated that mIL1 alpha but not pIL1 alpha was r eleased in response to heat shock with biochemical and pharmacological prop erties similar to those reported for the stress-mediated release pathway ut ilized by fibroblast growth factor (FGF)1. However, unlike the FGF1 release pathway, the IL1 alpha release pathway appears to function independently o f synaptotagmin (Syt)1 because the expression of a dominant-negative form o f Syt1, which represses the release of FGF1, did not inhibit the release of mIL1 alpha in response to temperature stress. Interestingly, whereas the e xpression of both mIL1 alpha and FGF1 in MH 3T3 cells did not impair the st ress-induced release of either polypeptide, the expression of both pIL1 alp ha and FGF1 repressed the release of FGF1 in response to temperature stress . These data suggest that the release of mIL1 alpha requires proteolytic pr ocessing of its precursor form and that mIL1 alpha and FGF1 may utilize sim ilar but distinct mechanisms for export.