Molecular and functional characterization of an IL-1β receptor antagonist in grass carp (Ctenopharyngodon idella)

In the present study, we discovered a novel IL-1 family member (nIL-1F) from grass carp that possessed the ability to bind with grass carp IL-1β receptor type 1 (gcIL-1R1) and attenuate grass carp IL-1β activity in head kidney leukocytes (HKLs), suggesting that it may function as an IL-1β receptor antagonist. Grass carp nIL-1F transcript was constitutively expressed with the highest levels in some lymphoid organs, including head kidney, spleen and intestine, implying its potential in grass carp immunity. In agreement with this notion, in vitro and in vivo studies showed that nIL-1F mRNA was inductively expressed in grass carp with a rapid kinetics, indicating that it may be an early response gene during immune challenges. In addition, recombinant grass carp IL-1β (rgcIL-1β) induced nIL-1F mRNA expression via NF-κB and MAPK (JNK, p38 and p42/44) signaling pathways in HKLs. Particularly, the orthologs of nIL-1F found in other fish species, including zebrafish, pufferfish and rainbow trout are not homologous to mammalian IL-1β receptor antagonist (IL-1Ra), indicating that fish nIL-1F and mammalian IL-1Ra may not share a common evolutionary ancestor. Taken together, our data suggest the existence of a naturally occurring fish nIL-1F, which may function like mammalian IL-1Ra, being beneficial to understand the auto-regulatory mechanism of IL-1β activity in fish immunity.