Further aspects of IL-1β secretion revealed by transfected monkey kidney cells

Because the cytokine interleukin-1β (IL-1β) lacks a classical hydrophobic signal sequence, it has been unclear how it is released from cells, and whether release proceeds via a novel mechanism or through non-specific leakage. To address this issue, we have examined the secretion of the recombinant forms of human IL-1β from COS monkey kidney cells, which express low levels of endogenous IL-1β. Four proteins were expressed: precursor and mature IL-1β and precursor and mature IL-1β fused to an amino terminal hydrophobic signal sequence from human tissue plasminogen activator. By monitoring the appearance of a known cytosolic protein (ATP citrate lyase) in the medium, we find that the unmodified IL-1βs are non-specifically released in very small quantities from the cytosol. On the other hand, the signal sequence-modified IL-1βs are glycosylated and efficiently secreted by the ER/Golgi pathway. The secreted, modified-mature protein is also biologically active, suggesting that this pathway has been bypassed for reasons other than maintaining the structural integrity of IL-1β. More likely the alternative pathway is a critical aspect of IL-1 biology. The differences in kinetics and quantity of IL-1β release from monocytic and COS cells suggest that COS cells lack critical components for the rapid release seen in monocytes.