Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-γ production

We have recently reported the identification of four novel members of the interleukin-1 (IL-1) family which we designated as IL-1 homologue 1-4 (IL-1H1-4). These proteins exhibit significant sequence homology to other members of the IL-1 family. Of these homologues, only IL-1H4 (renamed IL-IF7b) was predicted to contain a propeptide domain and a caspase cleavage site. We now report that caspase-1 cleaves IL-IF7b at the predicted site to generate mature IL-IF7b. Caspase-4 was also able to process IL-IF7b, albeit inefficiently. Other caspases and Granzyme-B did not cleave IL-IF7b. Furthermore, adenovirus-mediated expression of IL-IF7b in HEK 293 cells led to in situ processing and secretion of mature IL-IF7b. In a screen to identify a potential receptor, both pro and mature IL-IF7b bound to the soluble IL-18 receptor alpha-Fc (IL-18Ralpha-Fc) but not to the soluble IL-1R-Fc or ST2R-Fc fusion proteins. Mature 1L-1F7b bound to the IL-18Ra-Fc protein with higher affinity than the pro form, although the affinities for both proteins were significantly lower than that observed for IL-18. Consistent with this observation, only IL-18 and not lL-1F7b induced IFN-gamma production by KG1a cells. We also report that pro and mature IL-IF7b form homodimers with association constants of 4 muM and 5 nM, respectively, suggesting biological relevance to 1L-1F7b processing. Finally, we have localized the expression of IL-IF7b protein in discrete cell populations including plasma cells and tumor cells. These data suggest that IL-IF7b may be involved in immune response, inflammatory diseases and/or cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.